Konjac Mannan and Ginseng Compositions and Methods and Uses Thereof

ABSTRACT

Described are a number of compositions, namely a konjac mannan mixture, a ginseng composition, and a composition comprising konjac mannan and American ginseng. Methods of use of these compositions are described including their use for reducing blood glucose in non-diabetic and diabetic individuals, as well as reducing postprandial blood glucose in such individuals. Applications in the treatment of hyperlipidemia, high blood pressure, an increase in nitric oxide, Syndrome X and cardiovascular disease are also described. Various other applications of the compositions and methods are also described.

FIELD OF THE INVENTION

The invention relates to compositions comprising Konjac-Mannan, Ginsengor both and methods of use and uses of these compositions, such as inlowering blood glucose including post-prandial and long-term effects. Inone aspect this invention is in the field of glucose and other heartdisease risk factors management. In one aspect the invention isconcerned with dietary approaches to such management. In another aspectit is concerned with compositions and methods of reducing blood glucose,specifically

BACKGROUND OF THE INVENTION

Abnormal glucose tolerance and insulin resistance are related tomultiple cardiovascular risk factors especially reduced HDL, elevatedserum triglycerides and hypertension (Liese et al. (1998)). Whenclustered these abnormalities increase the risk of coronary heartdisease (CHD) morbidity and mortality, an effect that is independent ofother conventional risk factors (Trevisan et al. (1998)). Co-ocurrenceis usually present in insulin-insensitive individuals (Himswarth (1936))and is often described in relation to visceral adiposity (Haffner et al.(1986)) and lack of physical activity (Helmrich 1991)). The estimatedprevalence ranges from 3% (Trevisan et al. (1998)) to approximately 30%(Liese et al. (1998); Reaven (1994)) depending on how this insulinresistance-dislipidemic syndrome is defined and in which population itis measured.

Hyperglycemia and diabetes are strong and independent risk factors ofboth all-cause and cardiovascular (CVD) mortality (Wing et al. (1998)).These links are more pronounced when the diabetes is associated withother unfavorable risk factors such as hyperlipidemia (Goldsmith et al.(1994)), hypertension (Burt et al. (1995)), or a cluster of metabolicdisorders (Stamler et al. (1993)). Since people with diabetes havealmost twice the risk of dying from CVD (69.6%) compared to people inthe general U.S. population (Gu et al. (1998)), the control of highglucose levels and other concomitant coronary heart disease (CHD) riskfactors represents the most effective approach to prevention (Savage(1996)). The importance of stronger nutrition-hygienic measures has beenstressed repeatedly for the public at large (Stamler et al. (1993);National Cholesterol Education Program: Second report of the expertpanel on detection, evaluation, and treatment of high blood cholesterolin adults (adult treatment panel II). Circulation. 1994; 89:1333-1445)).When these measures prove inadequate, an aggressive drug therapy isoften required to meet the conventional treatment guidelines (NationalCholesterol Education Program: Second report of the expert panel ondetection, evaluation, and treatment of high blood cholesterol in adults(adult treatment panel II). Circulation. 1994; 89:1333-1445)). In thegeneral population, this approach has been shown to be effective inlowering both the prevalence of hypertension (Burt et al. (1995)) andserum cholesterol levels (Johnson et al. (1993)), but has not reducedthe incidence of diabetes (Harris et al. (1998)).

Although it has been extensively described (Liese et al. (1998);Trevisan et al. (1998; Himswarth (1936); Haffner et al. (1986); Helmrichet al. (1994)), followed-up (Reaven (1994)), and had its prevalencedetermined (1,2), no specific recommendations for treatment of thissyndrome have been proposed by health agencies. In practice, initialtherapy of individual risk factors such as moderate dyslipidemia,hypertension or hyperglycemia is nonpharmacological. Treatment willoften include behavioral changes to reduce body weight, increasephysical activity, and moderate alcohol consumption. To achievenutritional goals, there are three main approaches: ahigh-carbohydrate/low-fat diet (National Cholesterol Education Program:Second report of the expert panel on detection, evaluation, andtreatment of high blood cholesterol in adults (adult treatment panel II)Circulation 89:1333-1445 (1994)), sharing calories betweenmonounsaturated fat and complex carbohydrate at the expense of saturatedfat (American Diabetes Association (ADA): Nutrition Recommendations andprinciples for people with diabetes mellitus. Diabetes Care 22:s42-s43(1999)), or supplementing a high-carbohydrate/low-fat diet with exercise(Stefanick et al. (1998)).

Tighter fasting and postprandial glycemic control results in aconsiderable reduction in CHD and all-cause mortality (Wei et al.(1998)), as well as fewer long-term microvascular complications both intype 1 (DCCT Research Group: The effect of intensive treatment ofdiabetes on the development and progression of long-term complicationsin insulin-dependent diabetes mellitus. The diabetes control andcomplications trial. New Engl J Med 329:977-986 (1993)) and type 2diabetes (UK Prospective Diabetes Study (UKPDS) Group: Effect ofintensive blood-glucose control with metformin on complications inoverweight patients with type 2 diabetes: UKPDS 34. Lancet 352:854-865,1998). Effective dietary strategies shown to decrease (This OUTpostprandialThis OUT) plasma glucose excursions include the use of highfibre and low glycemic index diets (Wolever et al. (1992); Jenkins etal. (1994)). The mechanism is presumed to involve slowing carbohydrateabsorption (Jenkins et al. (1994)). Based on recent population studiesthese types of diets have been shown to have a protective role inpreventing diabetes (Salmeron et al., Diabetes Care 20:545-550 (1997);Salmeron et al., JAMA 277:472-477 (1997)) and CHD (18). In the case ofclinical studies however, it is the viscous water-soluble fibers, whichincrease the viscosity of digesta in the human gut (Eastwood et al.(1992)) that reduce glucose and lipid CHD risk factors (Anderson et al.(1986)). Whether soluble fibre is able to reduce a cluster of riskfactors is speculative. Studies using soluble fibre as an adjunct toconventional treatment in individuals with two or more major CHD riskfactors are scarce (Uuistupa et al. (1984)).

Evidence suggests that fibre may also be used in a therapeutic role.Recent epidemiological findings confirm the relationship between highdietary fiber intake and lower risk of developing both diabetes(Salmeron et al. (1997); Salmeron et al. (1997)) and CHD (Rimm et al.(1996)). Soluble dietary fiber, in particular, has been shown clinicallyto reduce the need for insulin, (Landin et al. (1992)) improve glycemia(Aro et al. (1981)), and reduce serum LDL-cholesterol (Brown et al.(1999)). Its viscosity is proposed as an important mechanistic factor(Jenkins et al. (1978)). However, to date, there is no clearly effectivecomposition or method for reducing blood glucose.

SUMMARY OF THE INVENTION

The present inventor has determined that the addition of high-viscosityfiber, in the form of a konjac-mannan mixture, or ginseng, or acomposition comprising a konjac-mannan mixture and ginseng to a diet ofan animal enhances conventional treatment outcomes, such as for diabetesand coronary heart disease, assessed primarily by total/HDL cholesterol,fructosamine, and sBP and secondarily by total, LDL, and HDLcholesterol; apolipoprotein A-1 (Apo A-1), B (Apo B) and their ratio;glucose; insulin; and systolic blood pressure (dBP).

Accordingly, in one aspect the present invention provides a compositionof matter for reducing blood glucose comprising a konjac-mannan mixture.In another aspect of the invention, a sufficient amount of thekonjac-mannan mixture, when given to an animal preferably at anappropriate time, reduces blood glucose in the animal, preferablypostprandial blood glucose. Preferably the konjac-mannan mixturecomprises konjac-mannan and a substance capable of increasing theviscosity of konjac-mannan from 50% to about 250% of konjac-mannanalone. More preferably the substance comprises about 5% to about 45% byweight of one or more such substances, preferably polysaccharides.

According to one embodiment a composition as just mentioned comprises asthe one or more polysaccharides xanthan, carragenan, acetan, guar, orxyloglucana.

According to another embodiment a composition according to the inventioncomprises consitituents with the particle size larger than about 1,000angstroms. In one aspect such a composition is used in controllingcholesterol levels, preferably lowering cholesterol levels.

Preferably, compositions according to the invention are formulated intoa liquid, powder or formulated as part of a food. However, in anotherembodiment the compositions of the invention are formulated into pills,capsules and tablets

According to another aspect the present invention provides a method forreducing blood glucose in an animal comprising administering to theanimal a sufficient amount of a konjac-mannan mixture at an appropriatetime in order to reduce blood glucose, preferably postprandial bloodglucose, in the animal. Preferably the konjac-mannan mixture compriseskonjac-mannan and a substance capable of increasing the viscosity ofkonjac-mannan to from about 50% to about 250% of konjac-mannan alone,preferably the substance comprises from about 5% to about 45% by weightof one or more polysaccharides, more preferably the one or morepolysaccharides are selected from the group consisting of xanthan,carragenan, acetan, guar, or xyloglucana.

According to one embodiment of the method, the particle size of theconstituents of a mixture of the invention are larger than about 1000angstroms.

According to another embodiment of the invention, a mixture according tothe invention is administered orally in an amount of about 1 to about 4grams per day, preferably the mixture is administered either prior to ameal or during the meal.

According to yet another embodiment of the method of the invention theadministration of a mixture according to the invention is by a liquid, apowder, or as a part of a food product. In another embodimentadministration is by way of tablet, capsule or pill.

According to another aspect of the invention, there is provided acomposition of matter for reducing blood glucose comprising ginseng inone aspect of the invention a sufficient amount of ginseng, when givento an animal at an appropriate time reduces blood glucose, preferablypostprandial blood glucose, in the animal.

According to another aspect of the invention, there is providedcomposition of matter for reducing blood glucose comprising an extractof ginseng, preferably American ginseng, a sufficient amount of whichwhen given to an animal at an appropriate time reduces blood glucose inthe animal. According to any of the ginseng compositions, whether rootor extract, the ginseng is comprised of a ratio of protopanaxadiols(diols) relative to protopanaxatriols (triols) that is preferablygreater than about 1.0, most preferably about 1.5 or greater and morepreferably about 1.90 or greater. In another embodiment, the diol/triolratio is about 2.4 or greater. In one embodiment, the composition isformulated into a liquid, powder or formulated as part of a food. Inanother embodiment the composition is formulated into tablets, capsulesor pills.

According to another aspect of the present invention there is provided amethod for reducing blood glucose in an animal comprising administeringto the animal a sufficient amount of ginseng at an appropriate time inorder to reduce blood glucose in the animal. In another aspect, there isprovided a method for reducing blood glucose in an animal comprisingadministering to the animal a sufficient amount of an extract of ginsengat an appropriate time in order to reduce blood glucose in the animal.According to either of these latter mentioned methods, preferably theginseng or extract is administered before a meal or with a meal, morepreferably the administration before meal occurs from about 1 to about180 minutes before the meal.

According to one embodiment of the method of the invention the amount ofginseng or extract of ginseng is at least about 1000 mg peradministration. In another embodiment, the amount of ginsengadministered is between 1-9 g, preferably 1-4 g and most preferably 1-3g.

According to another embodiment of the method of the invention theginseng comprises a ratio of diols/triols of greater than about 1.0,most preferably about 1.5 or greater and more preferably about 1.90 orgreater. In another embodiment, the diols/triols ratio is about 2.4 orgreater.

According to yet another embodiment of the method of the invention thecomposition is administered as a food, a powder, or a liquid. In anotherembodiment the composition is formulated into tablets, capsules orpills.

According to another aspect of the present invention there is provided acomposition of matter for reducing blood glucose comprising akonjac-mannan mixture of the invention and ginseng. In one embodiment ofthe invention a sufficient amount of konjac mannan and ginseng whichwhen given to an animal at an appropriate time reduces blood glucose inthe animal. Preferably the konjac-mannan mixture comprises konjac-mannanand a substance capable of increasing the viscosity of konjac-mannanfrom 50% to about 250% of konjac-mannan alone. Preferably the substancecomprises about 10% to about 40% of one or more polysaccharides. Morepreferably the one or more polysaccharides are xanthan, carragenan,acetan, guar, or xyloglucana.

According to one embodiment according to this aspect of the inventionthe particle size of constituents within the mixture is larger thanabout 1,000 angstroms.

According to another embodiment according to this aspect of theinvention the American ginseng is comprised of a ratio of diols/triolsof greater than about 1.0, most preferably about 1.5 or greater and morepreferably about 1.90 or greater. In another embodiment, the diol/triolratio is about 2.4 or greater. According to yet another embodimentaccording to this aspect of the invention the composition is formulatedinto a liquid, powder or formulated as part of a food.

According to another embodiment, the ginseng used in the compositionsand methods of the invention can be any ginseng or extract thereof, forinstance American, Asian, Chinese or other ginseng known in the art. Inanother embodiment, the ginseng is preferably American ginseng. In yetanother embodiment of the invention, the ginseng or extract thereof hasa diol/triol ratio of about 1.0, most preferably about 1.5 or greaterand more preferably about 1.90 or greater. In another embodiment, thediol/triol ratio is about 2.4 or greater.

In another embodiment, the invention provides a method for determiningwhether a ginseng or extract thereof would be useful in controlling,modulating or lowering blood glucose, preferably postprandial bloodglucose, by determining the diol/triol ratio of the ginseng or extractand selecting for one that has a diol/triol ratio of about 1.5 orgreater. The selected extract can then be optionally tested for suchactivity using the traditional tests and assays described herein orknown in the art. In another embodiment, the selected ginseng can alsobe tested and selected for insulin, lipid profile, cholesterol and bloodpressure control, modulation or decrease. In yet another embodiment theselected ginseng can be tested and selected for effectiveness in thetreatment of diabetes and/or cardiovascular disease.

According to another aspect of the present invention the compositionsand methods of the invention can be applied to the treatment of longterm diabetes, heart disease, and syndrome X. In addition thecompositions and methods of the invention provide methods for increasinginsulin sensitivity in an animal and of treating type 2 diabetes as wellas for reducing systolic blood pressure or blood cholesterol and otherlipids and apolipoproteins

The details of the preferred embodiment of the present invention are setforth in the accompanying drawings and the description below. Once thedetails of the invention are known, numerous additional innovations andchanges will become obvious to one skilled in the art.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be better understood with reference to the drawingsin which:

FIG. 1 is a histogram illustrating the effect of various fibresincluding Konjac mannan alone on glucose response in individuals ineleven individuals in comparison with a Konjac-mannan mixture of thepresent invention.

FIG. 2 is a graph illustrating the post-meal blood glucose response ofindividuals histogram illustrating the effect of various fibresincluding Konjac mannan alone in comparison with a Konjac-mannan mixtureof the present invention.

FIG. 3 is a bar graph illustrating the composition of the placebo versuskonjac biscuits used in Example 10.

FIG. 4 illustrates the effect of konjac mannan versus placebo on bloodglucose levels as described in Example 10. FIG. 4A is a linear graphillustrating glucose response to a test breakfast before 3-weektreatment and FIG. 4B is a linear graph illustrating glucose response toa test breakfast after the 3 week treatment. FIG. 4C is a bar graphillustrating glucose area under the curve (AUC) before and after the3-week treatment.

FIG. 5 illustrates the effect of konjac mannan versus placebo on bloodinsulin levels as described in Example 10. FIG. 5A is a linear graphillustrating insulin response to a test breakfast before 3-weektreatment and FIG. 5B is a linear graph illustrating insulin response toa test breakfast after the 3 week treatment. FIG. 5C is a bar graphillustrating insulin area under the curve (AUC) before and after the3-week treatment.

FIG. 6 illustrates the effect of highly refined konjac mannan versus thekonjac mixture of the invention as described in Example 11. FIG. 6A is alinear graph illustrating absolute blood glucose levels. FIG. 6B is alinear graph illustrating incremental blood glucose levels. FIG. 6C is abar graph illustration glucose area under the curve.

FIG. 7 is a linear graph illustrating the results of Example 12 for theeffect of konjac mannan, American ginseng and both konjac mannan andAmerican ginseng on systolic blood pressure.

FIG. 8 illustrated the effect of konjac mannan and ginseng treatmentversus the separate treatments on blood glucose. FIGS. 8 A and B arelinear graphs illustrating blood glucose levels versus time and changestherein as described in Example 13.

FIG. 9 is a linear graph illustrating insulin levels versus time usingvarious treatment regimes: placebo, ginseng, konjac mannan mix, andkonjac mannan mix and ginseng.

FIG. 10 is a bar graph illustrating the effect of various ginsengpreparations with various diol/triol ratios on postpranial blood glucoselevels.

FIG. 11 illustrates a comparison of incremental change (linear graphs11A, C, and E) and area under the curve (AUC) (FIGS. 11B, D, and F) inplasma glucose (FIGS. 11A and B), insulin (FIGS. 11C and D) and nitricoxide (Nox) (FIGS. 11E and F).

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

As described above, the present invention is related to compositions andmethods for reducing blood glucose. In particular, the present inventorhas found that a konjac mannan mixture, a ginseng composition, or acomposition comprising konjac mannan and ginseng are effective in thereduction of blood glucose. In another embodiment, the compositions ofthe invention are effective in controlling or modulating the lipidprofile of an animal, blood pressure and insulin levels. Thecompositions of the invention A enhances conventional treatmentoutcomes, such as for diabetes and coronary heart disease, assessedprimarily by total/HDL cholesterol, fructosamine, and sBP andsecondarily by total, LDL, and HDL cholesterol; apolipoprotein A-1 (ApoA-1), B (Apo B) and their ratio; glucose; insulin; and systolic bloodpressure (dBP).

As used herein “about” when referring to a value includes amounts thatare within the scope of scientific certainty or uncertainty. Suchamounts would include amounts that are effectively equivalent to thevalues stated. “About” when used in relation to diol/triol ratios meansplus or minus 10% of the value.

As used herein “animal” means any member of the animal kingdom includingpreferably humans.

As used herein “postprandial” means after any food intake.

As used herein “sufficient amount” or “effective amount” means an amountof a composition, substance or reactant to give an observable result,including desired results.

As used herein “appropriate time” means at a time at whichadministration of a substance or composition provides an observableresult.

As used herein “prior to a meal” means at any time after a meal andbefore a subsequent meal.

As used herein “during a meal” means at any time after the commencementof consumption of one or more pieces of food by an animal, and can becoincident with commencement, and before the end of consumption of allfood consumed by the animal, at one sitting or occasion and can becoincident with completion of consumption or immediately thereafter.

As used herein “a food” means any substance or composition of substancesor compounds which are consumed by an animal, preferably for somenutritional value.

As used herein “a meal” means the consumption of one or more morsels orpieces of a food in a sitting where a sitting is the time taken toconsume the one or more morsels or pieces of a food.

As used herein, “diol/triol ratio(s)” or “diols/triols” refers toprotopanaxadiols (diols) relative to protopanaxatriols (triols).

Konjac Mannan

Konjac (Amorphophalus Konjac C. Koch) is a perennial plant belonging tothe family Araceae. “Konnyaku”, which is made from the tuber of thisplant, has been used traditionally for food in Japan for several hundredyears. The predominant component of edible konnyaku is a glucomannancalled konjac mannan (KJM). Edible konnyaku is made from the konjacflour, which is obtained from the dried tuber of this plant. KJM flouris obtained by grinding the tuber root of the Amorphophallus Konjac C.Koch. plant and is traditionally used as a food and remedy in the FarEast. In addition to previous findings (Vuksan et al. (1999)), otherfindings have shown it to improve cholesterol levels (Arvill et al.(1995)), hypertension, and glycemia (Doi et al. (1979); Shima et al.(1982)).

Konjac-mannan was chosen as the fibre because it represents apolysaccharide with one of the highest viscosities (Kiriyama et al.(1972)). The physiologically active component is a high molecular weightglucomannan polymer, which, when taken as a supplement, has been shownto have effects in lowering lipids (Arvill et al. (1995); Terasawa etal. (1979); Venter et al. (1987)), systolic blood pressure (sBP) (Arvillet al. (1995)), and glycemia (Doi et al. (1979); Shima et al. (1982)).

Several techniques are known in the art for separating konjac mannanfrom konjac flour. In one, konjac flour is boiled in water, treated withFehling's solution to convert the mannan to its copper complex, and thelatter is decomposed again into the mannan after purification, asdisclosed in J. Agr. Chem. Soc. Japan, 6, 991-995 (1930). In another,konjac flour is extracted with water, impurities are removed byprecipitating with ethanol and redissolving the precipitate in waterseveral times, and drying the precipitate finally obtained to obtainpure konjac mannan, as disclosed in Bull. Chem. Soc. Japan, 49, 298-322(1927). Water-soluble konjac mannan capable of undergoing gelation whenheated in an aqueous alkaline solution may be used as described in U.S.Pat. No. 3,973,008. Briefly it is obtained by extracting the groundtuber of the konjac plant with water, separating insoluble matter,dialyzing the solids-free liquid against water and then lyophilizing thedialyzed liquid to remove water. A person skilled in the art would befamiliar with suitable konjac mannan preparation protocols for useherein. All such preparation methods are intended to be encompassedwithin the scope of the present invention.

The present invention provides an improved konjac mannan composition.

The konjac mannan composition or mixture of the invention preferablycomprises konjac mannan and a substance that can increase the viscosityof the konjac mannan by 50-250%. Accordingly, in one aspect the presentinvention provides a composition of matter for reducing blood glucosecomprising a konjac-mannan mixture. In another aspect of the invention,a sufficient amount of the konjac-mannan mixture, when given to ananimal preferably at an appropriate time, reduces blood glucose in theanimal, preferably postprandial blood glucose. Preferably thekonjac-mannan mixture comprises konjac-mannan and a substance capable ofincreasing the viscosity of konjac-mannan from 50% to about 250% ofkonjac-mannan alone. More preferably the substance comprises about 5% toabout 45% by weight of one or more such substances, preferablypolysaccharides.

According to one embodiment a composition as just mentioned comprises asthe one or more polysaccharides xanthan, carragenan, acetan, guar, orxyloglucana.

According to another embodiment a composition according to the inventioncomprises consitituents with the particle size larger than about 1,000angstroms. In one aspect such a composition is used in controllingcholesterol levels, preferably lowering cholesterol levels.

Preferably, compositions according to the invention are formulated intoa liquid, powder or formulated as part of a food. However, in anotherembodiment the compositions of the invention are formulated into pills,capsules and tablets

According to another aspect the present invention provides a method forreducing blood glucose in an animal comprising administering to theanimal a sufficient amount of a konjac-mannan mixture at an appropriatetime in order to reduce blood glucose, preferably postprandial bloodglucose, in the animal. Preferably the konjac-mannan mixture compriseskonjac-mannan and a substance capable of increasing the viscosity ofkonjac-mannan to from about 50% to about 250% of konjac-mannan alone,preferably the substance comprises from about 5% to about 45% by weightof one or more polysaccharides, more preferably the one or morepolysaccharides are selected from the group consisting of xanthan,carragenan, acetan, guar, or xyloglucana.

According to one embodiment of the method, the particle size of theconstituents of a mixture of the invention are larger than about 1000angstroms.

According to another embodiment of the invention, a mixture according tothe invention is administered orally in an amount of about 1 to about 4grams per day, preferably the mixture is administered either prior to ameal or during the meal.

According to yet another embodiment of the method of the invention theadministration of a mixture according to the invention is by a liquid, apowder, or as a part of a food product. In another embodimentadministration is by way of tablet, capsule or pill.

Ginseng

A main ingredient of the ginseng is saponin. Various saponin areincluded in this ginseng, specifically there are twelve known kinds ofginsenside-Ro, -Ra, -Rb1, -Rb2, -Rc, -Rd, -Re, -Rf, -Rg1, -Rg2, -Rg3,-Rh. These are the ones (ginsenside-Rb1, -Rb2, -Rc) containing sapogenenand protopanaxadiol, and the ones (ginsenside-Re, Rf, -Rg1, -Rg2)containing sapogenen and protopanaxatriol. The main saponin in the crudedrug is ginsenside-Rb1, -Rb2, -Rc, -Rg1. The ginsenside-Ro is the sameas chikusetsusaponin V, and the ginsenside-Rb1 is the same as saponin D.

Besides these, the ginseng contains essential oil of 0.05%,beta.-elemene, panacene (C₁₅H₂₄) and panaxynol as polyacetylene compoundand further contains choline, vitamin B complex, fatty acid etc.

There are known to be at least seven different types of ginseng and inthe present disclosure a preferred form is American ginseng. There aremany types of ginseng, American, Asian, and others known in the art, andvarious subspecies thereof. Not all have the same compositions ortherapeutic effects, even within the same species. Effectiveness canalso depend on the method of preparation of ginseng composition.

According to another embodiment, the ginseng used in the compositionsand methods of the invention can be any ginseng or extract thereof, forinstance American, Asian, Chinese or other ginseng known in the art. Inanother embodiment, the ginseng is preferably American ginseng. In yetanother embodiment of the invention, the ginseng or extract thereof hasa diol/triol ratio of about 1.0, most preferably about 1.5 or greaterand more preferably about 1.90 or greater. In another embodiment, thediol/triol ratio is about 2.4 or greater.

According to one embodiment of the method of the invention the amount ofginseng or extract of ginseng is at least about 1000 mg peradministration. In another embodiment, the amount of ginsengadministered is between 1-9 g, preferably 1-4 g and most preferably 1-3g.

In another embodiment, the invention provides a method for determiningwhether a ginseng or extract thereof would be useful in controlling,modulating or lowering blood glucose, preferably postprandial bloodglucose, by determining the diol/triol ratio of the ginseng or extractand selected for one that has a diol/triol ratio of about 1.5 orgreater. The selected extract can then be optionally tested for suchactivity using the traditional tests and assays described herein orknown in the art. In another embodiment, the selected ginseng can alsobe tested and selected for insulin, lipid profile, cholesterol and bloodpressure control, modulation or decrease. In yet another embodiment theselected ginseng can be tested and selected for effectiveness in thetreatment of diabetes and/or cardiovascular disease.

Ginseng, preferably American Ginseng (Panax quinquefolium L.) reducespostprandial blood glucose in nondiabetic and people with diabetes.Preferably at least 1000 mg of ginseng, preferably American ginseng isadministered together or before the meal (up to 180 min) to see aneffect on the postprandial blood glucose responses to a test meal. Whilein nondiabetic it is important to take ginseng before meal, in type 2diabetes, the effect is seen irrespective of time of consumption(together with meal or up to 180 min before meal).

Ginseng, such as American ginseng with a profile of diol/triol ratio ofgreater than about 1.0, most preferably 1.5 or greater and morepreferably 1.90 or greater. In another embodiment, the triols/diolsratio is about 2.4 or greater. In one embodiment the composition may beadministered in the same manner as described above to produce glucoselowering effects. Ginseng with a particular ginsenosides profile mayhave an effect on increased secretion of the first phase insulin,similar to conventional diabetic drugs.

Ginseng roots was selected by chemical composition analysis using HPLC.If ginseng extract is used, it can be prepared by the usual extractionprocedure, by using a water and alcohol solution in ratio between 40% to80% of water, with the rest being alcohol. Other ginseng, and extractpreparation procedures are known in the art.

The present invention shows for the first time, that ginseng (root orextract) with protopanaxadiols to protopanaxa triols ratio higher thanabout 1.0, most preferable 1.5, lowers the postprandial glycemicresponse in both healthy and diabetic individuals and in the long termreduces serum lipids and blood pressure and thus improves diabetescontrol. Not intending to be bound by a particular theory, studiesconducted by the present inventors indicate that ginseng may potentateinsulin secretion potentially through a modulation of autocoidmetabolism linked to nitric oxide production. However, gut mediatedhormone effects may play part in the mechanism of action of AM but thisarea has not yet been explored.

Konjac Mannan and Ginseng

The invention also comprises the administration of both ginseng (such asAmerican Ginseng (Panax quinquefolium L.) and konjac mannan, jointly. Acombination of selected ginseng, such as American Ginseng (Panaxquinquefolium L.) and Konjac-Mannan fiber (Amorpophallus Konjac k) actjointly to reduce postprandial blood glucose in people with Type 2diabetes more than each individual material. The efficacy is notattainable by either treatment. The ginseng can be any ginseng orformulation thereof, preferably as described above, more preferably thathas a diol/triol ratio of greater than about 1.5 or more. Thekonjac-mannan is preferably the konjac mannan mix as described above.The konjac mannan and ginseng can be prepared and administered inseparate compositions or can be formulated into one composition.

While not wishing to be bound by any particular theory, the possiblemechanism of action for the hypoglycaemic effect of konjac/ginseng is toincrease insulin secretion/sensitivity, and together with konjacmannan's ability to slow nutrient absorption and also improve insulinsensitivity these combined effects result in lower prolonged elevationof postprandial blood glucose and have applications in prevention andtreatment of diabetes and heart disease. Thus there are two products,operating through different pathways, that significantly reduce key riskfactors for diabetes and cardiovascular disease.

Compositions

For the purposes of administration by means other than incorporationwithin a food, the compositions described herein can be prepared by perse known methods for the preparation of pharmaceutically acceptablecompositions which can be administered to subjects, such that aneffective quantity of the composition of the invention is combined in amixture with a pharmaceutically acceptable vehicle, thereby allowing forthe administration of a sufficient amount of the composition. Suitablevehicles are described, for example, in Remington's PharmaceuticalSciences (Remington's Pharmaceutical Sciences, Mack Publishing Company,Easton, Pa., USA 1985). On this basis, the compositions include, albeitnot exclusively, solutions of the substances in association with one ormore pharmaceutically acceptable vehicles or diluents, and contained inbuffered solutions with a suitable pH and iso-osmotic with thephysiological fluids.

One would appreciate that the effective or sufficient amount of acomposition of the invention can vary depending on the individual, suchas sex, age, and weight of the individual, and/or severity of acondition, such as diabetes. It may also in certain cases vary on thetime of administration, i.e. post or pre meal and time it takes for thesubstance to clear or be metabolized by the body. It may also varydepending on whether the compositions are administered separately orwith another substance that may modulate the effectiveness of thecomposition. For instance the effective amount of konjac mannan may varydepending on whether it is administered alone or in conjunction with aginseng or another substance that may act synergistically with it. Itmay also vary depending on the concentration and mode of preparation ofthe konjac mannan being administered. The above similarly applied to theadministration of ginseng.

Such compositions in one aspect are administered orally, such as byliquid, powder or formulated as part of a food, such as a biscuit. Itcould be administered in the form of pills, capsules and tablets. Otherforms of administration may also be suitable.

Such composition can be used in the modulation or control, preferablydecrease, of blood glucose, preferably postprandial blood glucose. Inanother aspect the compositions of the invention can also be used tomodulate or control insulin levels in an animal, preferably decreasesuch levels. The compositions of the invention can also be used tomodulate a lipid profile of a patient in need thereof. They can also beused to modulate blood pressure, preferably to lower blood pressure. Ina preferred embodiment the invention can be used in the treatment ofanimals, preferably humans, in need of controlling their glucose levels,such as in the management and treatment of diabetes. In anotherembodiment, the compositions of the invention can be used in themanagement and treatment of cardiovascular disease and associatedconditions, such as high blood pressure, high cholesterol level. Inanother embodiment, the compositions of the invention, especially theginseng compositions, can be used to modulate or control nitric oxidelevels in an animal.

The following non-limiting examples are illustrative of the presentinvention:

EXAMPLES General Methods for Examples 1-4 Subjects

Eleven diabetic patients (5 men, 6 women) gave written informed consentto participate in the present study that was approved by the Human EthicCommittees of St. Michael's Hospital and the University of Toronto. Allhad hyperlipidemia, hypertension, and type 2 diabetes (mean serumC-peptide 701±351 pmol/L), with a minimum of three years since the onsetof all three conditions. They were taking medications to control each ofthe three risk factors, consuming a National Cholesterol EducationProgram (NCEP) Step 2 diet Executive Summary of the Third Report of theNational Cholesterol Education Program (NCEP) Expert Panel on Detection,Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA;285:2486-2497, 2001, not smoking, nor taking alcohol, and leadingsedentary lifestyles at recruitment. Two participants had a history ofatherosclerotic heart disease, but none had evidence of recentmyocardial infarction, unstable angina, or congestive heart failure.Exclusion criteria were a family history of premature CHD,hypothyroidism, renal, hepatic, or gastrointestinal disease. Table 1provides baseline demographic, anthropometric and clinicalcharacteristics of the study participants.

Study Design

The study employed a double-blind, placebo-controlled, cross-overdesign, where all subjects were maintained on the same dosage of theirmedications throughout. The study began with an 8 week baseline periodover which participants followed an NCEP Step 2 ad libitum diet:Executive Summary of the Third Report of the National CholesterolEducation Program (NCEP) Expert Panel on Detection, Evaluation, andTreatment of High Blood Cholesterol in Adults. JAMA; 285:2486-2497,2001, documented by three non-consecutive days of food records every twoweeks. This was followed by the experimental phase of the study thatconsisted of two successive 3 week treatment periods, separated by a twoweek washout interval over which another three day food record wasobtained. During the first treatment period, subjects were randomlyassigned to either the KJM+ (Step 2 metabolically controlled dietenriched with fiber) or the control treatment (the same diet enrichedwith wheat bran [WB] fiber). For the second treatment period, thesubjects were crossed-over. The study began with 5 subjects taking theKJM+ treatment and 6 the control.

Diet

Both treatments consisted of a three-day rotating Step 2 diet with threemeals per day provided under metabolic conditions. All foods werepre-weighed, packaged and couriered to participants for consumption athome or at work. The mean macronutrient profile conformed with a Step 2diet. Energy intakes for weight maintenance were provided according toLipid Research Clinics Tables with adjustment for physical activity (TheLipid Research Clinics Population Studies Data Book. Vol. 2. Theprevalence study-nutrient intake. Washington D.C.: Government printingoffice (NIH publication no. 82-2014) (1982)). Total dietary fiber wasadministrated at 2 g/412 kJ (100 kcal), with a mean daily intakeaccording to energy intake ranging from 24 g to a plateau of 50 g forthose consuming 2500 Kcal per day or more. The actual diet consumed ispresented in Table 2.

The two treatments differed only in the type of fiber. On the KJM+treatment, participants received KJM+ enriched biscuits, whereas on thecontrol treatment they received an equal quantity of wheat bran(placebo) biscuits. Subjects were instructed to take biscuits togetherwith an 8 oz beverage, 3 times daily as a snack, including once atbed-time. Both were produced and provided by Dicofarm S.p.A, Roma,Italy, (commercially available in Italy as “Dicoman®” biscuits). Theyhad similar nutrient profiles (Table 2) and were indistinguishable intaste and appearance. KJM+ biscuits contained approximately 15% KJMflour of which 69% was the active high viscosity glucomannan, 15% otherpolysaccharides, and 16% excipients by weight. The KJM flour mix used inthe biscuits comprised in % by weight: 69% KJM, 21% xanthan and 10%caragenan. Because KJM flour comprised half (1 g/412 kJ [100 kcal]) ofthe total fibre on the KJM+ treatment, approximately 0.7 g/412 kJ (100kcal) was glucomannan. Wheat bran biscuits, in contrast, had a lowerproportion of fiber than KJM+ biscuits (Table 3). Approximately 14 g/dayof wheat bran fibre derived from standardized American Association ofCereal Chemist hard red wheat bran was, therefore, added to the control(WB) diet to compensate for these fiber differences.

Any food from the metabolic diet together with study biscuits notconsumed was brought to the clinic for weighing to measure compliance.Dietary changes found to occur during the first three-week treatmentperiod were duplicated prior to food delivery for the second treatmentperiod for each participant.

Laboratory Methods

Serum blood samples were immediately separated and stored in fouraliquots at −70° C. after collection. They were thawed at the end of thestudy for analysis of total cholesterol, HDL, and triglycerides (TRIG)measured enzymatically (McNamara et al. (1987); Warnick et al. (1982)).LDL content was estimated by the formula of Friedewald et al.(Friedewald et al. (1972)). Apolipoprotein (Apo) A1 and B weredetermined by rocket immunoelectrophoresis (Fruchart et al. (1982)).Fasting blood glucose was analyzed by a hexokinase method using a CobasMira Autoanalyzer (Roche Diagnostic, Mississauga, Canada). Serumfructosamine was analyzed in triplicate using the Cobas Fara II (Lloydet al. (1984)) and plasma insulin in duplicate by radioimmunoassay withreagent from ICN Biomedicals, Inc. (Horsham, Pa.) (Livesey et al.(1980)). Finally, C-peptide was determined by radioimmunoassay (Kuzuyaet al. (1976)).

Physical measurements were obtained by standard techniques. Bloodpressure was taken and expressed as the mean of three measurements tothe nearest 2 mm Hg on both arms. Fasting body weight was determinedusing a beam scale in light clothing, with an emptied bladder and inbare feet. Waist and hip circumferences were measured by softnon-stretchable tape on the narrowest and widest parts of the trunk.

Energy and nutrient analysis of the diets was calculated using USDepartment of Agriculture data (The Agriculture Research Services.Composition of Foods, Agriculture Handbook No. 8. Washington, D.C., USDepartment of Agriculture, 1992). The nutrient composition of thetreatment biscuits was analyzed, using the Prosky method to determinefiber content (Prosky et al. (1985)

Statistical Analyses

Results are expressed as mean ±SEM, except for age, anthropometricmeasurements and nutrient intake (mean ±SD). Data were analyzed by theStatistical Analysis System (SAS) (SAS Institute Inc.: SAS/STAT User'sguide. Version 6, 4^(th) ed. Cary N.C.: SAS Institute Inc. 1989)).Differences in serum lipids, apolipoproteins, glycemia, blood pressureand body weight between the beginning (week-0) and end (week-3) of eachtreatment (control and KJM+) were assessed by two-tailed Student'st-test for paired data (PROC UNIVARIATE). Analysis of covariance(ANCOVA) with the facility of General Linear Model procedure (PROC GLM)was used to test for differences in these same parameters between thetwo treatments. Adjustment for multiple comparisons was made by theBonferroni-Hochberg procedure (Hochberg (1988)) for primary(fructosamine, total/HDL cholesterol ratio, and sBP) and secondary (bodyweight; total, LDL and HDL cholesterol; Apo A-1; Apo B; Apo A-1/B ratio;glucose; insulin; and dBP) endpoints separately. P-values for eachendpoint were ordered sequentially and contrasted with the correspondingadjusted comparison wise critical alpha (α) levels. Null hypotheses wererejected only if the p-values were less than their correspondingα-values (Hochberg (1988)). Control of individual variation from therepeat measures aspect of the design was addressed by incorporating therandom subject effect as well as the starting measurement. Diet, sex,and phase effects were also incorporated in this model. To test forconfounding effects of body weight on study parameters, Pearsoncorrelations were performed (PROC CORR procedure).

Example 1

All participants followed the experimental protocol with littledifficulty. According to three-day food records collected over thebaseline and washout periods, subjects ate their usual low-fat (<25%energy) and high-fiber (>27 g per day) diets (Table 3). In addition,during the treatment periods, returned food and biscuits from metabolicdiets indicated that subjects consumed an average of 93% and 95% of dietcalories prescribed on the KJM+ and control (WB) treatments respectivelyand 88% (137 g/day) KJM+ test and 91% (142 g/day) WB placebo biscuits.Consumption patterns translated into an insignificant decrease in bodyweight during both treatment periods (Table 4). There was no correlationbetween changes in weight and serum lipids, glucose or blood pressure(data not shown). The only side effect experienced was a transientcomplaint of flatulence and soft stools reported by 37% and 24% ofparticipants during the KJM+ and the control (WB) treatmentsrespectively, but none refused to continue the study.

Example 2

Blood lipids were improved during KJM+ treatment compared to control(Table 4). The primary lipid endpoint, total/HDL cholesterol, decreasedsignificantly by 5.7±2.3% (P=0.034, α=0.05) during the KJM+ treatmentcompared to an insignificant increase of 4.7±4.4% (P=0.316, α=0.017) oncontrol. The resultant between-treatment decrease of 10±4.0% on the KJM+treatment was significant (P=0.028, α=0.05). The secondary endpoints oftotal and LDL cholesterol also fell significantly by 16±2.7% (P=0.001,α=0.005), 25±3.9% (P=0.001, α=0.005), during KJM+ treatment compared to4.9±3.7% (P=0.20, α=0.006), and 4.8±5.9% (P=0.45, α=0.008) on control.Resultant between-treatment differences of 11±4.2% (P=0.025, α=0.005)and 19±6.8% (P=0.033, α=0.006), were insignificant, however, aftercorrection by the Bonferroni-Hochberg procedure. The combined fall intotal cholesterol and LDL on the KJM+ treatment indicatedreclassification of the lipid status of 6 of the 11 subjects fromelevated to normal cholesterolemia (<5.2 mmol/L) (2). Values for LDL,however, were derived from only 9 subjects, because two of the 11participants had serum triglycerides levels over 4.5 mmo/L, not allowingfor calculation by the Friedewald equation.

Similar results were observed for Apo B and the Apo B/A-1 ratio. DuringKJM+ treatment both fell significantly by 14±3.4% (P=0.002, α=0.006) and8.6±2.3% (P=0.004, α=0.007), compared to 3.0±5.0% (P=0.57, α=0.013) and3.0±4.8% (P=0.55, α=0.01) on control respectively. These changes,however, resulted in an insignificant between-treatment difference of11±4.3% (P=0.025, α=0.005) and 5.6±4.5% (P=0.24, α=0.008), aftercorrection by the Bonferroni-Hochberg procedure.

In contrast, such effects were not seen on HDL, Apo A-1, ortriglycerides. During KJM+ and control treatments, HDL and Apo A-1decreased insignificantly, for insignificant between treatment changes.Similarly, during both treatments, triglycerides increasedinsignificantly, with no significant difference between treatments.

Example 3

Improvements in glycemic control were observed on the KJM+ treatmentcompared to control (Table 4). The primary glycemic endpoint, serumfructosamine, was reduced insignificantly during both the KJM+ andcontrol treatments by 6.1±2.4% (P=0.03, α=0.025), and 0.5±1.4% (P=0.751,α=0.05) respectively, after correction by the Bonferroni procedure. Theresultant between treatment decrease of 5.7±1.7% on KJM+ wasnevertheless significant (P=0.007, α=0.017). No significant differencesbetween treatment regimes were seen for the secondary endpoints ofinsulin or glucose, although during the KJM+ treatment, fasting glycemiafell significantly by 11±3.0% (P=0.004, α=0.008) compared to 1.5±6.1%(=−0.804, α=0.013) on control.

Example 4

An improvement in blood pressure was also observed on the KJM+ treatmentcompared to control (Table 4). The primary blood pressure endpoint, sBP,decreased significantly on KJM+ supplementation by 5.5±1.4% (P=0.003,α=0.017), compared to 1.4±2.7% (P=0.62, α=0.03) on control, producing asignificant between-treatment difference of 6.9±2.5% (P=0.021, α=0.025)or 9.4±3 mm Hg. During both treatments, diastolic blood pressure (dBP),however, remained virtually unchanged with no significant differencebetween treatments. The result was a reclassification in sBP status frommoderately high to normotensive (<135 mmHg) in 5 of 11 subjects afterthe KJM+ treatment.

Discussion of Examples 1-4

Examples 1-4 illustrate that the addition of 0.7 g/412 kJ (100 kcal) ofhigh viscosity glucomannan (KJM mix) in biscuit form to conventional CHDtreatment (a low saturated fat diet combined with drug therapy) improvedmetabolic control beyond the effect of conventional treatment alone inhigh-risk individuals with type 2 diabetes. Amelioration in three majorCHD risk factors—hyperglycemia, hypertension, andhyperlipidemia—relative to a matched placebo control treatment asmeasured by the primary endpoints fructosamine, sBP, and total/HDLcholesterol respectively was observed. Differences between secondaryglycemic, blood pressure, and lipid endpoints were insignificant afteradjustment for multiple comparisons by the Bonferroni-Hochbergprocedure. With greater power derived from a larger sample size,significance might have been achieved in these cases.

To achieve similar metabolic benefits, the recent dietaryrecommendations of the American Diabetes Association have changed theiremphasis from encouraging carbohydrate and less processed fiber foods toincreased consumption of monounsaturated fat (American DiabetesAssociation (ADA): Nutrition Recommendations and principles for peoplewith diabetes mellitus. Diabetes care 22:S42-S43, 1999). Their reasoningis that fiber has only very modest effects on LDL cholesterol and doesnothing to raise HDL cholesterol levels. Nevertheless, the diet usuallyprescribed for the management of CHD risk factors in people withdiabetes resembles an NCEP Step 1 or 2 diet. The recommendations forthese diets are as follows: for Step 1, of total calories <30% fromtotal, <10% from saturated, and <10% from polyunsaturated, with <300mg/day of cholesterol and for Step 2 the same except <7% of caloriesfrom saturated fat with <200 mg/day of cholesterol. In the twowell-controlled clinical studies in this area, limitations of the dietsare evident. Hunninghake et al., following hypercholesterolemic subjectson a Step 2 diet for three months, found that LDL was reduced by only 5%(Hunninghake et al. (1993)). Schaefer and colleagues found a reductionin LDL in subjects provided a Step 2 diet on a metabolic basis to be asmuch as 17%, but with adverse effects on other lipid parameters and noeffect on total/HDL cholesterol ratio (Schaefer et al. (1995)). A highinter-subject variability in LDL reductions was also noticed. Thepresent results, however, showed that KJM+ treatment resulted in animprovement in lipid ratios. The suggestion is that a Step 2 dietsupplemented with KJM+ may confer additional benefits over this dietalone.

Lipids

Improvements in blood lipid control have previously been shown when Step2 diets were supplemented with soluble fibre from different dietarysources (Jenkins et al. (1993)) or fibre supplements (Anderson et al.(1986); Olson et al. (1997)). While such studies have reported reducedtotal and LDL concentrations, few, as has been the case for NCEP diets,have reported improved lipoprotein ratios. Out of the three lipid trialsthat used KJM+ (Arvill et al. (1995); Terasawa et al. (1979); Venter etal. (1987)) the former two did not show a significant change in theseratios. In contrast, Venter and coworkers (Venter et al. (1987)) found4.5 g/day glucomanan significantly improved both LDL and the LDL/HDLratio in 18 hypercholesterolemic subjects. The present examples showed amore significant 10±4.0% decrease in the total/HDL ratio were noticed onthe KJM+ treatment compared to control. The mechanism by which the KJM+supplemented biscuits had this lipid lowering effect is not clear. Whilenot wishing to be bound by any particular theory, possibilities includean inhibition of cholesterol absorption in the jejunum (Ebihara et al.(1989)) and bile acid absorption in the ileum (Kiriyama et al. (1974))or less postprandial stimulation of HMG CoA reductase (Jenkins et al.(1993)). Other options include the generation of short chain fatty acidsby colonic microflora, predominantly propionate, which may decreasehepatic cholesterol synthesis (Venter et al. (1990)).

Glycemic Control

Improvements in diabetes control after soluble fibre supplementationhave been shown (Morgan et al. (1990)). KJM, in particular, has beenshown to have a beneficial effect following both acute (Shima et al.(1982)) and long-term (Doi et al. (1979); Shima et al. (1982))administration. In the present invention KJM+ treatment compared tocontrol, a 5.7±1.7% reduction was observed in serum fructosamine, ashort-term marker of diabetes control, with no effect on either fastingglucose or insulin concentrations. These results were not altered byexcluding four subjects treated with insulin. An effect of the gelforming KJM+ on digestion may explain this finding. It has beensuggested that decreases in glucose and insulin levels after theconsumption of water-soluble fibers are related to slower rates of foodabsorption in the small intestine associated with increased viscosity(Ebihara et al. (1981)). KJM has been shown to have very high viscosity,approximately five times higher than guar gum (Ebihara et al. (1981))and considerably more than pectin (Venter et al. (1987)). Consequently,in some studies it has been given at half the dosage relative to theseother fibers (Ebihara et al. (1981)). The present inventors have furtherincreased the viscosity of KJM by the addition of polysaccharides suchxanthan, caragenan, acetan, guar or xyloglucena.

Blood Pressure

Finally, although few studies have demonstrated an effect of fibre onblood pressure, significant reductions both in sBP and dBP have beenreported after consumption of guar granulates (Landin et al. (1992)) andsoluble dietary fibre supplements (Alison et al. (1992)). The sameeffect has been shown for KJM, but only on sBP (Arvill et al. (1995)).This last finding agrees with the results set out in the presentexamples, in which KJM treatment significantly reduced sBP by 6.9%compared to control but did not affect dPB. The commonly recommended oatbran, in contrast, has been shown to affect neither systolic nordiastolic blood pressure (Swain et al. (1990)). While not wishing to bebound by any particular theory, a possible mechanism for the bloodpressure lowering effect of soluble fibers may involve increased insulinsensitivity (Anderson et al. (1986)), which may reduce blood pressure byinfluencing sodium absorption in the distal tubule, increasingsympathetic nervous system activity and peripheral vascular resistance(Modan et al. (1985)).

The effect of KJM+ fibre supplements on the three CHD risk factorspersist even in subjects who are taking conventional drug therapyconcurrently. Consistent with the findings set forth in the examples, acombination of fiber and drugs has been shown to be more effectiveclinically than the drug given alone in improving metabolic control.Toumilehto and coworkers (Tuomilehto et al. (1989)) found that theviscous soluble fiber guar gum and gemfibrozil administered togetherreduced total cholesterol and LDL/HDL ratio significantly more thangemfibrozil and placebo. Elsewhere this same effect has been noticed forblood glucose and blood pressure. A significant reduction was found inpostprandial blood glucose after consumption of sulfonylyurea(glibenclamide) and glucomannan with a test meal compared tosulfonylyurea alone with the same test meal (Shima et al. (1983)).Similarly, a significant decrease in diastolic blood pressure wasnoticed after administration of guar gum compared to placebo in patientsreceiving drug treatment for hypertension (Uuistupa et al. (1984)).Together these findings suggest that highly viscous soluble fibre mayaugment or potentiate the effect of drugs.

In conclusion, the application of KJM+ supplementation in the high-riskdiabetic study group of the examples demonstrated simultaneousimprovement in all three diet-modifiable risk factors, indicating areduction in overall CHD risk (Jenkins et al. (1995)). One of thebenefits is that KJM+ supplemented therapy may lower required drugdosages and improve overall cost-effectiveness and acceptability oftreatment. Although it is agreed that food should be the normal way toachieve an adequate fiber intake, fiber supplemented foods haveadvantages in the treatment of individuals at high risk for CHD andrepresent a possible intermediate step between diet and drug therapy.

General Methods for Examples 5-8 Subjects

278 free-living subjects were screened from the Canadian-MalteseDiabetes Study between the age of 45 and 65 years. This population isknown to have one of the highest rates of diabetes (Katona et al.(1983)). Thirty eight of them satisfied the initial inclusion criteria:impaired glucose tolerance (IGT) (World Health Organization DiabetesMellitus: Report of the World Health Organization Study Group. Technicalreport No. 727:9-15, 1985); clinical absence of CHD; body-mass index ofless than 30 kg/m²; not taking medications for hyperglycemia,hyperlipidemia or hypertension; not smoking; nor consuming more than twoalcoholic drinks per day. These subjects were further screened for thepresence of the full multiple metabolic syndrome (Trevisan et al.(1998)) (syndrome X). This included moderate hypertension (>135/85 andless than 145/95 mm Hg), dyslipidemia (low-HDL [levels below 0.9 mmol/Lfor men and 1.2 mmol/L for women], and elevated triglycerides [greaterthan 2.3 mmol/L and less than 4.5 mmol/L]). Based on power analysis fromthe previous study (Vuksan et al. (1999)) and Example 1, eleven subjects(5 men, 6 women) who qualified were recruited. In addition to meetingthe above criteria, their fasting (98±13 pmol/L) and 2-hour postprandial(439±68 pmol/L) plasma insulin levels was greater (p<0.05) than twostandard deviation of the initial screening pool (71±8 and 316±47 pmol/Lrespectively). All eleven also had moderately high serum cholesterol(between 5.2 and 6.7 mmol/L) and were sedentary, with a mean (±SD) ageof 55±4 years (range: 46-61 years); a BMI of 28±3 kg/m²; a waist-hipratio of 0.98±0.2 (waist: 96±12 cm) in men and 0.91±0.4 (waist: 87±19cm) in women. They gave written informed consent to participate in thecurrent study that was approved by the Human Ethic Committees of St.Michael's Hospital and the University of Toronto.

Study Design

The study employed a double-blind, placebo-controlled, cross-over designthat was identical to that used in the previous study (Vuksan et al.(1999)) and Example 1. It began with an 8-week baseline period duringwhich participants followed a National Cholesterol Education Program(NCEP) Step 2 (American Diabetes Association (ADA): NutritionRecommendations and principles for people with diabetes mellitus.Diabetes Care 22:s42-s43, 1999)) ad libitum diet, documented by threenon-consecutive days of food records every two weeks. This run-in phasewas included to eliminate possible effects of dietary change onmetabolic parameters. The experimental phase of the study followed. Thisconsisted of two successive 3-week treatment periods, separated by atwo-week washout interval over which a Step 2 diet was followed anddocumented by another three-day food record. During the first treatmentperiod, subjects were randomly assigned to either the KJM+ (Step 2metabolically controlled diet enriched with KJM+ fiber) or the controltreatment (the same diet enriched with wheat bran [WB] fiber). For thesecond treatment period, the subjects were crossed-over. Bloodcollection, weight, blood pressure, and waist and hip measurements weredone at the beginning and end of each 3-week treatment period. The studybegan with 5 subjects taking the KJM+ treatment and 6 the control.

Diet

Both treatments consisted of a three-day rotating Step 2 diet with threemeals per day provided under metabolic conditions. All foods werepre-weighed, packaged and couriered to participants for consumption athome or at work. The mean macronutrient profile closely conformed to aStep 2 diet (of calories <30% from total fat, <7% from saturated fat,and <300 mg/day cholesterol) (American Diabetes Association (ADA):Nutrition Recommendations and principles for people with diabetesmellitus. Diabetes Care 22:s42-s43, (1999)). Energy intakes for weightmaintenance were provided according to Lipid Research Clinics Tableswith adjustment for physical activity (24). Total dietary fiber wasadministrated at 1.5 g/100 kcal, with a mean daily intake according toenergy intake ranging from 24 g to a plateau of 40 g for those consuming2800 kcal per day or more. The actual diet consumed is presented inTable 5.

The two treatments differed only in the type of fiber. On the KJM+treatment, participants received KJM+ enriched test biscuits whereas onthe WB-control treatment they received an equal quantity of wheat brancontrol biscuits. Subjects were instructed to eat an equal amount ofbiscuits together with an 8 oz beverage, 3 times daily as a snack,including once at bedtime. Both were provided by Dicofarm S.p.A, Roma,Italy. They had similar nutrient profiles and were indistinguishable intaste and appearance. KJM+ biscuits contained approximately 10% KJMflour of which 69% was the active high viscosity glucomannan, 15% otherpolysaccharides, and 16% excipients by weight (Vuksan et al. (1999)).The KJM flour mixture of the KJM+ biscuits comprised 69%+17% xanthan, 9%caragenan, and 8% guar. Because KJM flour comprised half (0.75 g/100kcal) of the total fibre on the KJM+ treatment, approximately 0.5 g/100kcal (8-13 g/day) was glucomannan. Wheat bran biscuits, in contrast, hada lower proportion of total dietary fiber than KJM+ biscuits.Approximately 11 g/day of wheat bran fibre derived from standardizedAmerican Association of Cereal Chemist hard red wheat bran was,therefore, added to the WB-control diet to compensate for these fiberdifferences. Subjects were instructed to sprinkle the additional fiberon cereal, yoghurt, and/or other compatible foods to improvepalatability.

Any foods from the metabolic diet together with study biscuits notconsumed during the study were returned to the clinic for weighing tomeasure compliance. Dietary changes found to occur during the firstthree-week treatment period were duplicated in the diets for the secondtreatment period for each participant.

Laboratory Methods

Laboratory methods were identical to those used in (Vuksan et al.(1999)). In brief, blood samples were separated immediately and storedas serum in four aliquots at −70° C. after collection. They were thawedat the end of the study for analysis of total cholesterol, HDL, andtriglycerides measured enzymatically. LDL content was estimated by theformula of Friedewald et al. Apolipoprotein (Apo) A1 and B weredetermined by rocket immunoelectrophoresis. Fasting blood glucose wasanalyzed by a hexokinase method using a Cobas Mira Autoanalyzer (RocheDiagnostic, Mississauga, Canada). Serum fructosamine was analyzed intriplicate using Cobas Fara II and plasma insulin in duplicate byradioimmunoassay with reagent from ICN Biomedicals, Inc. (Horsham, Pa.).C-peptide was determined by radioimmunoassay.

Statistical Analyses

Results are expressed as mean ±SEM, except for age, anthropometricmeasurements and nutrient intake (mean ±SD). Data were analyzed by theStatistical Analysis System (SAS Institute, Cary, N.C.). Differencesbetween the diets were assessed by two-tailed Student's t-test forpaired data (univariate procedure). This same statistic also assesseddifferences in serum lipids, apolipoproteins, glycemia, blood pressureand body weight between the beginning (week-0) and end (week-3) of eachtreatment (WB-control and KJM+). Analysis of covariance (ANCOVA) withthe facility of General Linear Model (GLM) procedure was used to testfor differences in these same parameters between the two treatments.Control of individual variation from the repeat measures aspect of thedesign was addressed by incorporating the random subject effect as wellas the starting measurement. Diet, sex, and phase effects were alsoincorporated in this model. Adjustment for multiple comparisons was madeby the Bonferroni-Hochberg procedure (Hochberg (1988)). P-values foreach endpoint were ordered sequentially and contrasted with thecorresponding adjusted comparison-wise critical alpha (α) levels. Thenull hypotheses were rejected only if p-values were less than theircorresponding α-values.

Example 5

All participants followed the experimental protocol with littledifficulty. Returned food from metabolic diets indicated that subjectsconsumed an average of 96% and 95% of diet calories prescribed on theKJM+ and WB-control treatments respectively. Returned biscuits indicatedthey consumed 81% (97 g/day) of KJM+ and 86% (103 g/day) of WB-controlbiscuits. Consumption patterns translated into an insignificant decreasein body weight during both treatment periods with no difference betweentreatments (Table 6). The only side effect experienced was a transientcomplaint of flatulence and soft stools reported by 3 and 2 of theparticipants during the KJM+ and the WB-control treatments respectively,but none chose to discontinue the study.

Example 6

Blood lipids improved during KJM+ treatment compared to WB-control(Table 6). Total and LDL cholesterol fell significantly by 19±2.7%(P<0.0001) and 29±3.4% (P<0.0001) during KJM+ treatment compared to6.3±3.4% (P=0.088) and 6.6±5.0% (P=0.231) on control. Thebetween-treatment differences were 12.4±3.1% (P<0.005) and 22±3.9%(P<0.003) respectively. The combined fall in total cholesterol from6.2±0.3 to 5.0±0.2 mmol/L and LDL from 3.9±0.2 to 2.8±0.2 mmol/L on KJM+treatment indicated reclassification of the lipid status of the group (8of 11 subjects) from elevated to normal cholesterolemia (NationalCholesterol Education Program: Second report of the expert panel ondetection, evaluation, and treatment of high blood cholesterol in adults(adult treatment panel II). Circulation 89:1333-1445, 1994)). Similarresults were observed for Apo B. During KJM+ treatment Apo B fellsignificantly by 19±2.8% (P<0.0004) compared to 4.5±4.5% (P=0.34) oncontrol, for a significant difference of 15.1±4.3% (P<0.0004) betweenthe treatments.

In contrast, such effects were not seen on Apo A-1, or triglycerides.During KJM+ and control treatments, HDL decreased significantly on bothtreatments (8.5±2.2%, P<0.04 on KJM+ diet and 9.6±2.2%, P<0.003 onWB-control, with an insignificant between-treatment change (P=0.98).Similarly, during both treatments, triglycerides increasedinsignificantly, with no significant difference between treatments.

Despite this lack of effect of KJM+ treatment on HDL, Apo A-1, ortriglycerides, the decreases in total cholesterol and Apo B weresufficient to improve lipid ratios. During KJM+ treatment total/HDL,LDL/HDL and Apo B/A-1 ratios decreased by 11±3.0% (P<0.005), 22±3.7%(P<0.0002) and 13±3.0% (P<0.003) respectively. This compares to aninsignificant increase of 4.1±4.1% in total/HDL ratio, 0.2±6.3% inLDL/HDL ratio and 0.7±3.6% in Apo B/A-1 on WB-control. The resultantbetween-treatment differences were 15.2±3.4% (P<0.003) for total/HDLcholesterol, 22.2±4.1% (P<0.002) for LDL/HDL cholesterol, and 13.1±3.4%(P<0.0003) for Apo B/A-1.

Example 7

An improvement in glycemic control was observed on the KJM+ treatmentcompared to WB-control (Table 6). Serum fructosamine was reduced duringthe KJM+ treatment by 5.6±1.5% (P<0.003), compared to 0.39±1.3% (P=0.77)on control, with a between-treatment difference of 5.2±1.4% (P<0.002).No significant between-treatment differences were seen for insulin orglucose concentrations. On KJM+ however, fasting glycemia fell by13±2.5% (P<0.0001) compared to 9.6±4.3% (P<0.05) on control.

Example 8

No change in systolic or diastolic blood pressure was observed on eithertreatment or between treatments (Table 6).

All above results remained unchanged after adjustment for multiplecomparisons by the Bonferroni-Hochberg procedure.

Discussion of Examples 5-8

These Examples demonstrate that the addition of 0.5 g/100 kcal (8-13g/day) of high viscosity glucomannan in biscuit form to ahigh-carbohydrate/low-saturated fat NCEP Step 2 diet improved metaboliccontrol beyond diet alone in individuals with the insulinresistance-dyslipidemic syndrome. Significant reductions inhyperglycemia as measured by the short-term marker of glycemic control,fructosamine, were observed. Also observed were significant reductionsin hyperlipidemia as measured by total, LDL, LDL/HDL and total/HDLcholesterol, apo B and apo B/A-1, relative to a matched WB-controltreatment. These findings represent the first to demonstrate suchimprovements using soluble fiber in individuals with this particularcluster of risk factors that also includes the intermediate diabeticclassification, IGT, syndrome X.

Because of the strong implications of this syndrome, a more aggressiveapproach has been suggested to achieve similar reductions. Diabetes andheart disease share common precursors for the development ofatheroslerosis that often co-occur. Long before diabetes becomesmanifest, the clustering of metabolic abnormalities exerts a synergisticeffect on the atherosclerotic process (Haffner et al. (1990)). Based onfindings from Trevisea and colleagues, cardiovascular disease (CVD) riskappears to increase linearly with an increase in the number of theserisk factors. It is recommended therefore that insulin resistantpatients have their CHD risk factors managed as if they have establishedcoronary heart disease (Haffner et al. (1998)).

Low-fat/high carbohydrate diets may still have promise as a therapeuticapproach. Although there has been a shift away from their advocacy infavor of those rich in monounsaturated fat (American DiabetesAssociation (ADA): Nutrition Recommendations and principles for peoplewith diabetes mellitus. Diabetes Care 22:s42-s43, 1999), these dietssupplemented with fiber may have similar metabolic advantages. Guar gum,pectin, oat products, and psyllium added to high carbohydrate diets havebeen shown to improve total and LDL cholesterol significantly, with noimprovement to triglycerides and slight or no adverse effects on HDL(Jenkins et al. (1978)). Both guar (Aro et al. (1981)) and KJM+ (Arvillet al. (1995); Vuksan et al. (1999)) supplementation have also beenshown to improve other risk factors, including glycemia and bloodpressure. This lead to support for the use of guar in the treatment ofthe multiple metabolic syndrome (Landin et al. (1992)). Evidence furthersuggests that supplementation with these soluble fibers may augmentconcurrent drug therapy. Improvements in these assorted risk factorsfollowing supplementation have been noticed beyond what was achieved bydrugs alone in subjects receiving hypolipidemic (Aro et al. (1981);Vuksan et al. (1999); Tuomilehto et al. (1989)), hypoglycemic (Aro etal. (1981); Vuksan et al. (1999); Shima et al. (1983)), and hypotensive(Vuksan et al. (1999); Uuistupa et al. (1984)) medications.

The ability of soluble fiber to improve a high carbohydrate/low fat dietis supported by the findings of these Examples. Total and LDLcholesterol were decreased and glycemic control was improvedsignificantly. Also, although HDL, Apo A-1, and triglycerides wereunaffected, as has been noticed with other fibers, this was balanced bythe significant improvements in the other lipid endpoints, leading tosignificant reductions in all three lipid ratios: Total/HDL, LDL/HDL,and Apo B/A-1. Similar improvements in these ratios have rarely beenreported using dietary interventions (Tuomilehto et al. (1989); Shima etal. (1983)). Overall, the present findings indicate that a Step-2 dietsupplemented with KJM+ may confer additional benefits over the Step-2diet alone, benefits that may be comparable to strategies usingmonounsaturated fat.

KJM+ may be better suited than the other major soluble fibers inimproving outcomes with high-carbohydrate/low-fat diets. Althoughmeta-analyses use variance adjusted values that tend to underestimateeffectiveness, KJM+ can be compared to other soluble fibers in terms ofits lipid lowering ability per gram of fiber, using recentmeta-analytical data (Brown et al. (1999)). Daily intake of glucommananfrom KJM+ on this study produced an average net change in total and LDLcholesterol of −0.084 and −0.119 mmol/L per gram of fiber respectively.These reductions represent approximately triple the lipid loweringcapacity of psyllium (−0.028 and −0.029 mmol/L respectively), oatproducts (−0.037 and −0.032 mmol/L respectively), and guar gum (−0.037and −0.033 mmol/L respectively) (Brown et al. (1999)). In the case ofpectin, they represent comparable total cholesterol lowering capacity(−0.070 mmol/L) and approximately twice the LDL lowering capacity(−0.055 mmol/L) (Brown et al. (1999)). The very high viscosity of KJM+used in this present study may explain these differences. It has beenshown to be approximately five times higher than that of guar gum(Ebihara et al. (1989)) and beta-glucan (Wood (1990)), and considerablymore than that of pectin (Venter et al. (1987)).

Contributions made by its theological properties may offer insight intothe proposed mechanism by which the KJM+ supplemented biscuits had theirbeneficial effects. While not wishing to be bound to any particulartheory, possibilities for its lipid lowering action may include aninhibition of cholesterol absorption in the jejunum (Venter et al.(1987) and bile acid absorption in the ileum (Kiriyama et al. (1974))mediated by viscosity or less postprandial stimulation of HMG CoAreductase (Jenkins et al. (1993)). Other options include the generationof short chain fatty acids, predominantly propionate, by colonicmicroflora that may decrease hepatic cholesterol synthesis (Venter etal. (1990)). The improvement in glycemic control may be attributable toan effect of the gel forming KJM+ on rate of digestion. It has beensuggested that decreases in glucose and insulin levels after theconsumption of water-soluble fibers are related to slower rates of foodabsorption in the small intestine associated with increased viscosity(Jenkins et al. (1978)). This mechanism may explain why a reduction inserum fructosamine, but did not concomitant reductions in fastingglycemia and insulinemia were observed: KJM+ may be exerting its effectmainly postprandially.

In conclusion, the results in these Examples support the role of KJM+mix as a means for improving high-carbohydrate diets in the ameliorationof the insulin resistance-dyslipidemic syndrome. Improved metaboliccontrol resulted in the correction of several risk factors thatcharacterize the syndrome and figure prominently in the etiology ofatherosclerotic CHD.

Example 9 Effect of Various PolySaccharides on Blood Glucose

Ten healthy male (3) and female (6) volunteers (Age=37; BMI=26.3 kg/m²)were randomly assigned to consume either wheat bran control, psylliumfiber, xanthan, KJM alone (FMC Co.) or KJM mix (preparation: KJM 74%,xanthan 26%) on five separate occasions. Each of the treatmentscontained 5 grams of above-mentioned ingredients which was added to 75 gavailable carbohydrate (300 ml) derived from glucose drink Glucodexsolution (Technolab, Quebec) drink. Capillary blood glucose was takenafter 10-12 hrs fasting and 15, 30, 45, 60 and 90 minutes after start ofthe test meals. Blood glucose was analyzed using YSI 2300 instrument.Results are presented as area under the glucose curve (FIG. 1) andabsolute and incremental blood glucose levels (FIG. 2) for individualtime points. The results indicated that the area under the glucose curvefor KJM mix (39) was significantly lowered (P<0.011) than controltreatment (113; p<0.02), psyllium (100; p<0.032), xanthan (81; p<0.041)and KJM alone (80; p<0.027). Incremental and absolute glucose levelswere significantly reduced on KJM mix treatment at time 30 (P<0.05)compared to all other treatment.

In summary, FIGS. 1 and 2 provide illustrations of the significanteffects on blood glucose a konjac mannan mixture of the presentinvention has over the effects of individual saccharides and konjacmannan alone. The mixture of konjac mannan comprised konjac mannan andxanthan although, other saccharides which can be use include,carragenan, acetan, guar, or xyloglucana.

Example 10 Chronic Feeding of Konjac-Mixture and Effect on PostprandialGlycemia in Insulin Resistance

Atherosclerosis and diabetes have been characterized as postprandialphenomena. Recent epidemiological analyses demonstrated that diets witha low glycemic load reduce their incidence. To investigate the abilityof KJM mix to reduce postprandial glycemia in the insulin resistancesyndrome (syndrome X) that underlies these diseases, 12 participantswere studied (age: 55±4 y, BMI: 28±3 kg/m²) who satisfied the criteriafor the syndrome (IGT, reduced-HDL, elevated triglycerides andmild-hypertension) following 21 days of KJM mix supplementation. In acrossover design, participants were assigned to take a metabolicallycontrolled NCEP Step-2 diet either with 0.7 g/100 kcal of KJM mixenriched biscuits (as outlined in Examples 5-8), or matched wheat brancontrol biscuits over two 21 day treatment periods (see FIG. 3 forcomposition profiles). Venous blood samples were drawn at 0, 30, 45, 60,90, 120, and 180 min after a standard breakfast (see Table 7), before(day-1) and after (day-3) chronic feeding of the KJM mix or wheat branbiscuits on each treatment period. Plasma glucose [FIG. 4A (day-1), FIG.4B (day-3)] and insulin [FIG. 5A (day-1) and FIG. 5B (day-3)]concentration profiles were determined and whole body insulinsensitivity was calculated using both fasting and postprandial values,according to Matsuda and DeFronzo (Diabetes Care 1999; 22:1462-70). Areaunder the curves for glycemia (−23.5% versus 0.4±2.3%, P=0.000022) (FIG.4C) and insulinemia (−40.5±4.5% versus −2.0±2.9%, p=0.000012) (FIG. 5C)were significantly reduced on the KJM mix treatment compared to wheatbran control treatment. These decreases translated into a significantincrease in postprandial insulin sensitivity on KJM compared to control(55.9±9.2% versus 9.7±4.5%, P=0.00056). Insulin sensitivity index (ISI)was calculated as follows:

Composite Whole Body ISI=10,000/(FPG×FPI)×(G×I)

Where 10,000 is the constant; CompositeWhole Body ISI is hepatic &peripheral tissue insulin sensitivity, FPG is fasting plama glucose(mg/dL); FPI is fasting plasma insulin (μU/ml); G is mean glucose afterglucose challenge; and I is mean insulin after glucose challenge.

From this it may be concluded that prolonged consumption of KJM improvesglycemic control, as indicated by lower postprandial glycemia andinsulinemia.

Example 11 Effect of Highly Refined Konjac Mannan and Konjac Mannan Mixon Postprandial Glycemia in Normal Individuals

To determine the effect, if any, of viscosity of KJM fiber preparationson KJM activity, the efficacy of the KJM mix compared with highlyrefined commercially available KJM RS (Opta Co., US) on loweringpostprandial blood glucose levels was studied.

First viscosity measurements were taken of 2 KJM fibers, commerciallyavailable highly purified KJM RS produced by Opta C. (KJM 3) and thesame KJM mixed with 23% of xanthan (KJM 1). To determine the differencein viscosity over time, 1.5 g of each KJM sample was mixed with 150 mlof water. Theological measurements using a Synchro-electric Viscometer(D.W. Brookfield Ltd., Cooksville, ON) (Shear 0.6/12, spindle E) weretaken at 15, 30, 45, 60, 90, 120, 180 min and 24 h. Relative viscositywas compared between the samples. The two KJM fibres from Opta Co. (KJM3) or the KJM mix (KJM 1) were compared in vivo testing. In vitroanalysis indicated that viscosity of KJM 1 (KJM mix) was significantlyhigher (42,000 cps) compared to commercially available most purifiedkonjac RS fibre, KJM 3 (16,200 cps).

For the in vivo study seven healthy male (4) and female (3) volunteers(Age=43; BMI=24.7 kg/m²) were randomly assigned to consume either wheatbran control, KJM RS (KJM 3) or KJM mixture treatment containing 23% ofxanthan gum (KJM 1) on three separate occasions. Each of the treatmentscontained 3 grams of above-mentioned ingredients which was added to 50 gavailable carbohydrate (356 ml) derived from vanilla flavored Ensure™drink (Ross Abbott Laboratories). Capillary blood glucose was takenfasting (i.e after a 10 to 12 hrs fast) and 15, 30, 45, 60 and 90minutes after start of the test meals. Blood glucose was analyzed usingYSI 2300 instrument. Results are presented as area under the glucosecurve (FIG. 6C) and absolute and incremental blood glucose levels (FIGS.6A and 6B) for individual time points. The results indicate that thearea under the glucose curve for KJM 1 (68.4) was significantly lowered(by about 44%) (P<0.015) than control treatment (120.5), and KJM 3(P<0.034) treatment (95.6) (lowered by about 21%). There weresignificant differences between the two KJM fibers on time. Incrementaland absolute glucose levels were significantly reduced on KJM 1treatment at time 60 (P<0.02) and 90 minutes (P<0.01) as compared to KJM3 treatment. When compared to the control meal KJM 3 showed nosignificance difference at any time points, or for the area under theglucose curve. As such it can be concluded that KJM mixed withpolysaccharides such as xanthan in proportion to act synergistically ismore effective on postprandial glycemia than highly refined KJM alone.KJM in mixture with other polysaccharides will express its efficacy inglycemic control of healthy individuals.

Example 12 Effect of American Ginseng, Konjac Mannaan Mix andCombination Thereof on Postprandial Blood Pressure in Type 2 Diabetes

The effect of the proprietary KJM MIX, AG, and their combination (AG&KJMMIX) on postprandial blood pressure regulation in type 2 diabeticindividuals as compared with wheat bran control was studied. Seventeenhealthy male (10) and female (7) volunteers (Age=64.7; BMI=29.4 kg/m²)were randomly assigned to consume either wheat bran control, AG, KJMmixture treatment containing 27% of xanthan gum (KJM MIX), orcombination of AG and KJM MIX, on four separate occasions. Each of thetreatments contained 3 grams of above-mentioned ingredients which wasadded to 50 g available carbohydrate (356 ml) derived from vanillaflavored Ensure™ drink. Standardized lunch was served at 240 minutestime after start of breakfast. Blood pressure was taken −30 min, 0, 30,60, 120, 240, 360, and 420 minutes after start of the test meals. Bloodpressure was determined using conventional mercury sphygmomanometerdevice. Results are presented as systolic and diastolic blood pressure(See FIG. 7). When compared to the control treatment, systolic bloodpressure (SBP) was significantly reduced after taking KJM MIX (at time30, 60, 120, and 360 minutes); KJM MIX and AG combined (at 30, 60, 120,and 240 minutes), whereas AG lowered SBP only at 30 min and 120 minafter start of test breakfast. The diastolic blood pressure was notdifferent between four treatments. Therefore, it can be concluded thatKJM MIX and AG whether taken alone or in combination reduce SBP in type2 diabetic individuals. Further, the effect of the combination of KJMand AG seems to be different than each individual component. Thisindicates that there is a different mechanism of action which might bebeneficial and superior to either of the two components alone.

Example 13 Effect of American ginseng, Konjac Mannan Mix and CombinationThereof on Postprandial Blood Pressure, Blood Glucose and Insulin inType 2 Diabetes

The effect of the proprietary KJM MIX, AG, and their combination (AG&KJMMIX) on postprandial blood pressure, blood glucose and insulinregulation in type 2 diabetic individuals as compared with wheat brancontrol was studied.

Seven volunteers with type 2 diabetes were recruited; duration ofdiabetes 8.4±4.9 yr, HbAlc 6.9±1%, 86.4±15.9 kg. The study utilized acrossover, double blind design. Four sets of breakfasts and lunches wereadministered in random order. Lunch was a standard meal, only thebreakfast meal contained either wheat bran (control) or KJM mix with orwithout AG. The test days were randomized for each subject and werescheduled at least one week apart. The total test day spanned 7 hours.Blood samples were taken using an indwelling catheter at −30, 0, 5, 10,15, 30, 45, 60, 90, 120, 150, 180, 240 (lunch), 270, 300, 330, 360, 390and 420 min. Samples will be analyzed for glucose and insulin.

Clinical blood pressure was measured using conventional mercurysphygmomanometer according to Joint National Council (JNC) VI criteriaat −30, 0, 30, 60, 120, 240, 360, 420 min. Subjects were asked to recordtheir satiety levels throughout the day using a bipolar scale rangingfrom −3 (extremely hungry), 0 (neutral), to +3 (uncomfortably full). Thepalatability of the meals was also recorded on a scale from 1 to 10,where 1 was “dislike extremely”, 5 “neutral” and 10 “delicious”. At eachvisit weight was measured using a beam scale and total body fat wasmeasured with the Futrex 5000, using infrared technology. Additionalsamples were taken at the beginning and end of the study and measuredfor hemoglobin levels. This measurement was suggested by the EthicalBoard of St Michael's Hospital as there was a concern regarding possibleanemia.

The results indicated that weight and total body fat did notsignificantly differ for each intervention. Hemoglobin decreasedsignificantly by 12.2 g/L. There were no differences between meals inpalatability of either breakfast or lunch. The blood pressure resultslook promising.

Postprandial blood glucose was significantly lower in all 3interventions (KJM mix, AG, and its combination) compared to controlwheat bran. The lowest results are found to be with combination of KJMmix and AG, indicating an additive effect of mixing the two compounds(FIGS. 8A and 8 b). Insulin results indicated significantly higherinsulin secretion, but lower on KJM mix and even lower when 2 compoundswere combined. (FIG. 9)

Overall, the effect of KJM, and AG in the present study confirmed thatthey both beneficially affect postprandial glycemia. Postprandial bloodglucose was lowered by two mechanisms that are different butcomplementary; ginseng increase insulin secretion and KJM mix reducesinsulin levels (increases insulin sensitivity). The effect of thecombination of KJM and AG seems to be different than each individualcomponent. This indicates that there is a different mechanism of actionwhich might be beneficial and superior to either of the two componentsalone. The fact that blood glucose was lowest on KJM mix and AGcombination with lowest insulin secreted, indicate that this combinationprovides the most effective and economic intervention of all three.Saving insulin (insulin economy) to achieve lowest blood glucose resultswould be extremely beneficial in a diabetes therapy.

Example 14 The Effect of Protopanaxadiol/Protopanaxatriol Ratios ofGinseng on Glucose Levels

There are a wide variety of ginsengs and not all, even ones within thesame species will necessarily have the same effect. As such thecomposition profiles of various ginsengs and their effect on bloodglucose and insulin was studied.

The effect of ginsengs with different diols/triols ratios wasinvestigated. In series of successful clinical studies American ginsengwas used, with composition of protopanaxadiols (Rb₁, Rb₂, Rc, and R)(diols) relative to protopanaxatriols (Rg₁, Re, Rf) (triols), that had aratio of above approximately 1.5 (i.e. Chinese ginseng with 1.91 ratioand American with 1.51 and 2.44 ratio). As such ginseng with a specificginsenoside profile significantly decreases glucose. Ginseng profileswith weight ratios lower than 1.5 were also studied.

In the studies, ginseng was given with a 75 g oral glucose tolerancetest (OGTT) and compared the results to a similar study done previouslywith ginseng with higher ratios (FIG. 10). Normal subjects were studiedwith 3 different ginsengs; in a first study 12 (gender: 6 m: 6 f, age:31±3 years, BMI: 28±2 kg/m²) with Chinese ginseng with diols/triolsratio of 0.8; in the second and third studies, 10 (gender: 4 m: 6 f,age: 41±6 years, BMI: 26.1±0.4 kg/m²) with AG with diols/triols ratio of1.2 and 1.37, respectively. A single-blind, crossover design was used inwhich all subjects received control or 6 g, 40 min before a 75 g-OGTT.Control in the present study consisted of identical capsules containingcornstarch, whereas in the previous study it was the 75 g-OGTT donealone. Both protocols followed the Canadian Diabetes Associationguidelines for the OGTT, with venous blood samples drawn at −40, 0, 15,30, 45, 60, 90, and 120 min. Repeated measures analysis of variancedemonstrated that there was no significant effect of the AG containingdiols/triols ginsenosides with ratios lower then 1.5. on incrementalchange or area under the curve (AUC) for glycemia or insulinemia. Thatwas in contrast with results where ginseng with ratios aboveapproximately 1.5 had beneficial effects. One of the explanation forthis discrepancy is that the level of total or specific activeginsenosides, possibly in diols fraction rather than triols fraction ofginseng. These data suggest that the ginsenoside profile of ginseng,particularly ratio between protopanaxadiols to protopanaxatriols ofabove 1.5, so this play a role in its effects.

That part of ginseng's profile that gives improvement in humanmetabolism seems to be related to ginseng composition, mainly to ratiosbetween main ginsneosides groups. The ginsenoside content of the 6different ginseng grinded root and extracts used in the series ofclinical studies was studied and found that reduction of blood glucose,lipids, and blood pressure; and also increase in insulin secretion, andnitric oxide, and reduction in oxidative stress had a high proportion ofprotopanaxadiols (Rb₁, Rb₂, Rc, and Rd) relative to protopanaxatriols(Rg₁, Re, Rf).

The present study indicates that an optimal level of this ratio ofginseng to be effective should be higher then approximately 1.5 (FIG.10).

In FIG. 10, each bar represents ginseng with different diols/triolsratio. Once a ratio is reached of approximately 1.5 or higher thepostprandial blood glucose is significantly reduced (letter b vs. a ongraph). The first bar (area=167) is Chinese ginseng root with ratio 0.8.The second bar (area=196) is American ginseng extract (75% water:alcohol25%) with ratio 1.2. The third bar (area=159) is American root ginsengwith ratio 1.37. The fourth bar (area=159) is American root ginseng withratio 1.37. The fifth bar represents (area=129) Chinese ginseng extract(59% water:41% alcohol) and ratio of 1.91 and this reduced blood glucosesignificantly. The sixth bar represents (area=142) American root ginsengwith ratio 1.51 and this also reduced blood glucose significantly. Theseventh bar represents (area=109) American ginseng root with ratio 2.44and this reduced blood glucose significantly.

A further pilot study in healthy volunteers was conducted to explore theeffect of the whole root ginseng versus an alcohol:water=55:45 extract,both with diols to triol ratio>1.5 with or without the addition of KJMmix. Results showed that both ginseng types and the KJM lowered theincremental glucose area and combining the ginseng with the KJM mix hadan additional effect (results not shown).

Example 15 The Effect of American Ginseng on Insulin and Nitric Oxide

Other metabolic benefits such as increase in insulin secretion andnitric oxide generation (FIG. 11) are demonstrated with ginseng withratio of above 1.5. In this study ginseng had ratios of diols/triols of2.44. Ginseng was administrated to 8 (gender: 3 m: 5 f, age: 34±3 years,BMI: 24.6±0.8 kg/m²) healthy individuals. Data presenting reduction ofpostprandial blood glucose, and increase in plasma insulin and nitricoxide generation, relative to control. Data are presented in FIG. 11.

Comparison of incremental change and area under the curve (AUC) inplasma glucose, (FIG. 11A, 11B), insulin (FIGS. 11C and 11D) and nitricoxide (NOx) (FIGS. 11E and 11F) following ginseng (diols/trialsratio=2.44)) taken 40 min before (Δ) or together (◯) with a 75 g oralglucose tolerance test (75 g-OGTT) or a 75 g-OGTT done alone previously(□) in 8 non-diabetic subjects. Glucose and insulin were measured byglucose oxidase method (67) and double antibody radioimmunoassay methodrespectively (68). Plasma NOx was measured as total nitrite (NO₂⁻)+nitrate (NO₃ ⁻) concentrations by the chemiluminescence method(69,70) using a Sievers 280 NO Analyzer (Boulder Colo., USA). Points orbars with different letters are significantly different (repeatedmeasures ANOVA adjusted for multiple pairwise comparisons with theNewman Keuls procedure, P<0.05). Data are mean ±SEM.

Example 16 Effect of Ginseng on Postprandial Glycemia

The present inventor conducted four studies to determine the effect ofAmerican ginseng in humans were conducted (Table 8).

In the first of these studies, the glycemic responses in 10 normal and 9type 2 diabetic subjects was studied after the administration of 3 gAmerican ginseng or placebo given 40 minutes before (−40 minutes) ortogether with a 25 g oral glucose challenge. It was observed thatselected blood glucose concentrations and the area under the curve werereduced significantly when ginseng was administered either before ortogether with the challenge compared to placebo in the diabetic subjectsand only when given before in the normal subjects (Vuksan, Arch. Intern.Med 2000; 160:1009-13.

Similar reductions in postprandial glycemia both in nondiabetic anddiabetic subjects were observed, in three subsequent acute dosing andtiming response studies that followed (Table 8). The first of these twostudies showed that 3, 6, or 9 g of American ginseng compared to placebosignificantly reduced the postprandial glycemic response to a 25 g oralglucose challenge when administered 0 (together with), 40, 80, or 120minutes before a glucose challenge in 10 diabetic subjects (Vuksan,Diabetes Care 2000; 23:1221-6) and when administered 40, 80, or 120minutes before the challenge in 10 nondiabetic subjects (Vuksan, J AmColl Nutr 2000: 18:738-744). There were no differences observed ineither study between the doses or the times of administration in theirglycemic lowering effect. These data suggested that ginseng is equallyeffective at doses above 3 g and when administered at any time togetheror before the challenge in diabetic subjects, but only when administered40 minutes or more before the challenge in nondiabetic subjects. Thethird study showed that 1, 2, or 3 g of American ginseng compared toplacebo reduced significantly the postprandial glycemic response to a 25g oral glucose challenge when administered 40 minutes but not 20, 10, or0 minutes before a glucose challenge in 12 nondiabetic subjects (VuksanAm. J. Clin Nutr,). Again there were no differences detected between thedoses studied. The suggestion was that ginseng is equally effective atdoses above 1 g, but needs to be administered a minimum of 40 minutesbefore the challenge in nondiabetic subjects.

Having illustrated and described the principles of the invention in apreferred embodiment, it should be appreciated to those skilled in theart that the invention can be modified in arrangement and detail withoutdeparture from such principles. We claim all modifications coming withinthe scope of the following claims.

All publications, patents and patent applications referred to herein areincorporated by reference in their entirety to the same extent as ifeach individual publication, patent or patent application wasspecifically and individually indicated to be incorporated by referencein its entirety.

TABLE 1 Baseline Characteristics of the Study Subjects According to Sex*MEN WOMEN CHARACTERISTICS (N = 5) (N = 6) Age - yr 62 ± 8  59 ± 7 Bodyweight - % desirable† 133 ± 33  143 ± 22 Android obesity - prevalence‡ 54 Baseline values: Serum total cholesterol - mmol/L 6.2 ± 0.4  5.9 ± 0.5Glycosylated hemoglobin - % 7.4 ± 2.1 8.3 ± 3  Systolic/Diastolicpressure - mm Hg: 139/78  136/82 Known duration of: Diabetes - yr(self-reported) 11.5 ± 9   18.1 ± 6   Hypertension - yr 7.1 ± 3   6.0 ±2  Hyperlipidemia - yr 6.3 ± 3   5.6 ± 2  Drug/insulin treatment -prevalence: Insulin 1 3 Sulfonylurea and/or Metformine 5 6 Diuretics 2 4Other hypothensive 4 3 Lipid lowering medications§ 5 6 *Except for drugtreatment, blood pressure, and android obesity values are expressed asmean ± SD. To convert values for cholesterol to mg/dl multiply by 38.67.†Values were assessed from Metropolitan Life Insurance tables, 1983.‡Android obesity is indicated by a wait-to-hip ratio grater than 0.9 formen, and 0.8 for women §Bile acid sequestrant, nicotinic acid and/orcoenzyme A reductase inhibitor

TABLE 2 Average Intake of Energy and Nutrients in Eleven Subjects Beforeand During Study Periods.* Parameters Baseline† Konjac-mannan Wheat BranP‡ Total energy, kJ/d 7671 ± 1760  8907 ± 2250  9134 ± 1006 .23 Totalfat, % of energy 24.8 ± 6.2  23.4 ± 2.1 23.9 ± 1.6 .6 Saturated fat, %of energy 8.2 ± 2.4 4.1 ± .4 3.9 ± .2 .73 Monounsaturated fat, % ofenergy 7.3 ± 1.3 12.4 ± 1.9 12.6 ± 1.4 .35 Polyunsaturated fat, % ofenergy 9.1 ± 2.1 7.1 ± .2 7.6 ± .3 .24 Cholesterol, mg/4184 kJ 87 ± 17 44 ± 18  36 ± 11 .12 Total protein, % of energy 18.7 ± 4.2  15.5 ± 1.714.9 ± 2.1 .86 Available carbohydrate, % of energy 56.5 ± 14.3 60.5 ±8.6 61.2 ± 6.5 .4 Sugar, % of energy 13.2 ± 17.2 11.2 ± .6  10.4 ± .3 .17 Total fiber, g/d 27.4 ± 14.2  39.3 ± 11.4  40.1 ± 12.5 .9 Watersoluble, g/d 8.1 ± 2.7 23.1 ± 4.1  8.3 ± 2.4 <.001 Water insoluble, g/d17.8 ± 4.2  16.7 ± 3.6 29.8 ± 4.8 <.001 Sodium, mg 4540 ± 1350 2820 ±348 2708 ± 420 .878 Potassium, mg 1430 ± 850  3960 ± 450 4240 ± 664 .659Calcium, mg 630 ± 442 1150 ± 185 1370 ± 246 .552 *Values are mean ± SD.Konjac-mannan and wheat bran diets are based on actual intake. Toconvert kJ to kcal multiply by 2.39. †Based on the mean of fournon-consecutive 3-day food records. ‡Differences between thekonjac-mannan and wheat bran study periods were calculated by studentspaired t-test.

TABLE 3 Composition (g/100 g) of Konjac-mannan (KJM) and Wheat Branbiscuits, at the moisture content of 2.8 g/100 g. Total Dietary FiberGlucomannan Biscuits Available from KJM Energy^(§) Type Protein FatCarbohydrate* KJM flour Ash Dietary Fiber^(H) flour^(I) (kJ/100 g) WheatBran 6.8 14.4 66.5 — 1.4 2.8 — 1011 Konjac-mannan 6.2 13.9 61.2 15.3 1.32.3 10.6 944 *Values are calculated by difference: 100 − (moisture +protein + fat + total dietary fiber + ash). Sucrose added is between37-40% of total available carbohydrate. ^(H)Average values for dietaryfiber in wheat bran and flour analyzed by method of Prosky et al.(1985). ‡ Value represents 64% glucomannan polymer derived from KJMflour. ^(§)Values for available carbohydrate expressed asmonosaccharide. To convert kJ to kcal multiply by 2.39.

TABLE 4 Changes in Serum Lipids, Glycemia, Blood Pressure, Body Weightand 10-yrs. Coronary Heart Disease (CHD) Relative Risk during andbetween the Konjac-mannan and Control (Wheat Bran) Study Periods*.Konjac-mannan Wheat Bran Between-Treatments Risk factors Week-0 Week-3Change, % Week-0 Week 3 Change, % Change, % P Cholesterol, mmol/L Total6.10 ± 0.29 5.11 ± 0.28  −16 ± 2.7§ 5.81 ± 0.19 5.48 ± 0.19 −4.9 ± 3.7 −11 ± 4.3  0.0252 LDL 3.89 ± 0.25 3.04 ± 0.26  −25 ± 3.9§ 3.56 ± 0.183.29 ± 0.16 −4.8 ± 5.9  −19 ± 7  0.0331 HDL 1.07 ± 0.08 0.94 ± 0.06  −11± 2.2‡ 1.04 ± 0.10 0.95 ± 0.08 −8.9 ± 2.4‡ −2.2 ± 3   0.4924Triglyceride, 2.53 ± 0.23 2.88 ± 1.38 18.7 ± 12.8 2.69 ± 0.44 2.96 ±0.37 25.1 ± 14.7 −6.4 ± 14   0.6565 mmol/L Apolipoprotein, g/L Apo A-11.47 ± 0.07 1.37 ± 0.06   −6 ± 3.1 1.48 ± 0.08 1.48 ± 0.10 +0.7 ± 3.7 −6.7 ± 4.3  0.1541 Apo B 1.50 ± 0.09 1.28 ± 0.08  −14 ± 3.4‡ 1.48 ± 0.081.40 ± 0.07 −3.0 ± 5.0  −11 ± 4  0.0253 Lipid Ratios: Total/HDL 6.08 ±0.48 5.69 ± 0.48 −5.7 ± 2.4† 6.06 ± 0.56 6.21 ± 0.53 4.7 ± 4.4 −−10 ±4   0.0279 Apo B/Apo A-1 1.05 ± 0.09 0.96 ± 0.08 −8.6 ± 2.3‡ 1.05 ± 0.100.99 ± 0.08 −3.0 ± 4.5  −3.2 ± 5   0.2353 Glycemia: Glucose, mmol/L 9.63± 0.80 8.62 ± 0.95  −11 ± 3‡ 9.29 ± 0.74 8.99 ± 0.78 −1.5 ± 6.1  −9.7 ±4   0.1413 Fructosamine, 3.43 ± 0.1  3.17 ± 0.2  −6.1 ± 2.4† 3.25 ± 0.2 3.25 ± 0.2  −0.5 ± 1.4  −5.7 ± 1.7  0.0069 mM Insulin, pmol/L  154 ±38.6  150 ± 32.8 9.58 ± 9.7 142 ± 31  140 ± 31  2.1 ± 11  −7.5 ± 12  0.559 Blood pressure, mm Hg Systolic 139.5 ± 5.0  131.6 ± 4.9  −5.5 ±1.4‡ 128.8 ± 4.0  130.4 ± 4.7  1.4 ± 2.7 −6.9 ± 2.5  0.0211 Diastolic79.1 ± 2.0  77.5 ± 1.8  −1.6 ± 2.8 78.3 ± 1.6  78.4 ± 2.7  0.4 ± 3.6 −2± 5  0.7056 Body weight, kg 85.6 ± 19   85.0 ± 19   −0.6 ± 0.5 85.9 ±19   85.3 ± 19   −0.6 ± 0.4  −0.1 ± 0.4  0.8991 CHD Realtive 1.77 ± 0.2 1.50 ± 0.2   −14 ± 2.7§ 1.56 ± 0.2  1.63 ± 0.3  8.7 ± 7.3 −22 ± 4.7 0.0107 Risk (10 yr) *Except body weight (mean ± SD) values are expressedas mean ± SEM. Abbreviations are defined as LDL, low-densitylipoprotein; HDL, high-density lipoprotein; Apo, apolipoprotein. Toconvert cholesterol, triglycerides, and glucose to mg/dl multiply by38.67, 88.57, and 18, respectively. To convert insulin to μU/ml,multiply by 0.1394. All means are for n = 11 except for LDL where n = 9,since two subjects had triglycerides above 4 mmol/L preventingcalculation by Friedewald equation. Within treatment differences wereassessed by paired t-test [(†) P < .05; (‡) P < .01; (§) P < .001],while between treatment differences by ANCOVA (PROC GLM). Lack ofnotation indicates no significant differences. [(†&) P < .05; (‡$) P <.01; (§#) P < .001],

TABLE 5 Average Intake of Energy and Nutrients Before and During StudyPeriods in Eleven Subjects Parameters Baseline KJM WB Total energy(kcal/d) 2 070 ± 700   2 579 ± 628   2 355 ± 420   Total fat (% ofenergy) 30.5 ± 4.3 29.3 ± 3.2 28.7 ± 2.4 Saturated fat  7.2 ± 4.7  6.7 ±0.8  6.4 ± 0.7 (% of energy) Monounsaturated 10.3 ± 5.1 12.7 ± 2.1 12.2± 2.6 fat (% of energy) Polyunsaturated 13.0 ± 5.7  9.9 ± 1.8 10.1 ± 0.9fat (% of energy) Cholesterol (mg/d)  328 ± 102 219 ± 48 236 ± 77 Totalprotein 14.6 ± 8.2 16.2 ± 2.7 15.6 ± 3.2 (% of energy) Available 54.9 ±21  54.5 ± 9.4 55.7 ± 7.3 carbohydrate (% of energy) Sugars (% ofenergy) 13.3 ± 3.6 11.2 ± 0.9  9.2 ± 1.4 Total fiber (g/d) 24.2 ± 11 34.7 ± 8.4 33.4 ± 9.6 Water soluble (g/d)  6.9 ± 3.2 23.4 ± 1.7  9.9 ±3.2* Water insoluble (g/d) 17.3 ± 7.3 11.2 ± 3.8  23.1 ± 2.6* Sodium(mg)  5 810 ± 2 384 3 162 ± 648   3 380 ± 647   Potassium (mg) 3 882 ±713   4 530 ± 611   4 840 ± 872   Calcium (mg) 1 366 ± 193   1 260 ±238   1 487 ± 446  

TABLE 6 Changes in Serum Lipids, Glycemia, Blood Pressure, and BodyWeight during and between the Konjac-mannan (KJM) and Wheat Bran Control(WB-Control) Study Periods in Eleven Subjects KJM WB-ControlBetween-Treatments Risk factors Week-0 Week-3 Change, % Week-0 Week-3Change, % Change, % P* Cholesterol (mmol/L) Total 6.2 ± 0.3 5.0 ± 0.2  −19 ± 2.69* 6.0 ± 0.2 5.6 ± 0.2 −6.3 ± 3.36 −12.4 ± 3.1  0.0038* LDL3.9 ± 0.2 2.8 ± 0.2   −29 ± 3.37* 3.8 ± 0.2 3.5 ± 0.2 −6.6 ± 5.04 −22.3± 3.9  0.0017* HDL 1.0 ± 0.1 0.9 ± 0.1  −8.5 ± 2.19* 1.0 ± 0.1 0.9 ± 0.1 −9.6 ± 2.24* 1.2 ± 2.2 0.9812 Triglyceride 2.8 ± 0.2 3.0 ± 0.2 10.1 ±9.92 2.9 ± 0.4 3.0 ± 0.3 12.1 ± 14   −1.6 ± 10   0.7317 (mmol/L)Apolipoprotein (g/L) Apo A-1 1.4 ± 0.1 1.4 ± 0.1  −6.5 ± 2.46* 1.5 ± 0.11.4 ± 0.1 −4.8 ± 3.38 −1.8 ± 3.1  0.3622 Apo B 1.6 ± 0.1 1.3 ± 0.1   −19± 2.78* 1.6 ± 0.1 1.5 ± 0.1 −4.5 ± 4.47 −15.1 ± 4.3  0.0003* LipidRatios: Total/HDL 6.5 ± 0.5 5.7 ± 0.4   −11 ± 3.02* 6.2 ± 0.4 6.4 ± 0.54.14 ± 4.16 −15.2 ± 3.4  0.0023* Apo B/Apo A-1 1.1 ± 0.1 1.0 ± 0.1   −13± 3.02* 1.1 ± 0.1 1.1 ± 0.1 0.72 ± 3.61 −13.1 ± 3.4  0.0002* LDL/HDL 4.2± 0.4 3.2 ± 0.3   −22 ± 3.72* 3.9 ± 0.3 3.9 ± 0.4 0.22 ± 6.27 −22.2 ±4.1  0.0012* Glycemic Control: Glucose (mmol/L) 6.8 ± 0.5 5.9 ± 0.3  −13 ± 2.48* 6.6 ± 0.3 5.9 ± 0.4 −9.6 ± 4.27 −3.8 ± 3.6  0.7653Fructosamine  286 ± 13.6  269 ± 11.9  −5.6 ± 1.46*  279 ± 11.7  278 ±12.6 −0.39 ± 1.3  −5.2 ± 1.4  0.0013* (mM) Insulin (pmol/L) 94.8 ± 16.691.1 ± 16.5 0.91 ± 8.88 99.2 ± 16.5 88.5 ± 11.4 −3.0 ± 9.67 3.9 ± 8.90.9683 Blood pressure (mm Hg) Systolic 139 ± 2.0  135 ± 3.6  −2.9 ± 1.88135 ± 2.6  138 ± 3.7  2.2 ± 2.5 −5.1 ± 2.2  0.448 Diastolic 85.4 ± 1.8 84.8 ± 1.5  −0.26 ± 2.55  85.5 ± 1.7  86.5 ± 1.5  1.33 ± 1.49 −1.4 ±2.1  0.2647 Body weight (kg) 80.7 ± 5.1  80.6 ± 5   −0.17 ± 0.14   81 ±5.3 80.6 ± 5.1  −0.29 ± 0.35  0.1 ± 0.2 0.5303

TABLE 7 Test Breakfast Compositions Placebo Breakfast Konjac Breakfast49 g W. Bran Cookies 58 g Konjac Cookies 52 g Branflakes 69 g Branflakes250 ml 2% Milk 250 ml 2% Milk 8 g Butter 8 g Butter MacronutrientComposition Energy (Kcal) 673 678 Protein (%) 10.3 11.2 Total Fat (%)29.0 28.6 Available Carbo (%) 61.1 59.2 Total Fiber (g) 13.0 13.1Soluble Fiber (g) 7.2 1.4

TABLE 8 AUC Study Sample Treatments OGTT Reductions P value Study 1 10NGT 3 g AG vs placebo @ 0 min 25 g — P = NS (Age: 34 ± 7years, 3 g AG vsplacebo @ −40 min 18% P < 0.05 BMI: 25.6 ± 3 kg/m²) 9 T2DM 3 g AG vsplacebo @ 0 min 25 g 19% P < 0.05 (Age: 62 ± 7years, 3 g AG vs placebo @−40 min 22% P < 0.05 BMI: 29 ± 5 kg/m², HbA_(1c): 7.6 ± 0.5%) Study 2 10NGT Dosing: 3, 6, or 9 g AG vs placebo 25 g 26.6, 29.3, P < 0.05 (Age:41 ± 13years, 38.5% for 3, 6, BMI: 24.8 ± 3.5 kg/m²) and 9 g Timing: −40min vs −120 or −80 min — P = NS Study 3 10 T2DM Dosing: 3, 6, or 9 g AGvs placebo 25 g 19.7, 15.3, 15.9 P < 0.05 (Age: 63 ± 2years; % for 3,6,and BMI: 27.7 ± 1.5 kg/m²; 9 g HbA₁c: 7.3 ± 0.3%) Timing: −120, −80, −40or 0 min — P = NS Study 4 12NGT Dosing: 1, 2, or 3 g AG vs placebo 25 g14.4, 10.6, 9.1 P < 0.05 (Age: 42 ± 7 years, % for 1, 2, and BMI: 24.1 ±1.1 kg/m²) 3 g Timing: −40 min vs −20, −10 or 0 min 14.1, 15.0, 9.2 P <0.05 % for −40 min AG, NGT, OGTT, T2DM, NS denote American ginseng,normal glucose tolerance, oral glucose tolerance test, type 2 diabetesmellitus, and nonsignificant respectively. P-values are for repeatedmeasures analysis of variance (ANOVA) comparisons between absolutevalues. Values are mean ± SD.

DETAILED LEGENDS OF THE TABLES Table 1 * Except for drug treatment,blood pressure, and android obesity values are expressed as mean ±SD. †Values were assessed using Metropolitan Life Insurance tables, 1983. ∀Android obesity is indicated by a wait-to-hip ratio grater than or equalto 0.9 for men, and 0.8 for women § Bile acid sequestrants and/orHMG-coenzyme A reductase inhibitors. Table 2 * Values are mean ±SD.Konjac-mannan and wheat bran diets are based on actual intake. † Basedon the mean of four 3-day food records. ‡ Differences betweenKonjac-mannan and wheat bran study periods were calculated by studentst-test for paired data. Table 3

* Values are calculated by difference: 100−(moisture+protein+fat+totaldietary fiber+ash). Added sucrose was between 37-40% of total availablecarbohydrate.

† Average values for dietary fiber in wheat bran and flour analyzed bymethod of Prosky et al., 1985. ‡ Value represents 69% glucomannanpolymer derived from KJM flour. Table 4 * Except for body weight (mean±SD), all values are expressed as mean ±SEM. † Between treatmentdifferences assessed by ANCOVA (PROC GLM) ‡ Comparisonwise alpha (α)level was adjusted for multiple endpoint comparisons with theBonferroni-Hochberg procedure for primary and secondary endpointsseparately.

§ Significant after adjustment of alpha level by the Bonferroni-Hochbergprocedure. Null-hypotheses were rejected only if the p-values were lessthan their corresponding α-value. P-values for during treatment changeswere assessed by paired t-test ∥ LDL values are for nine subjects, sincetwo subjects had triglycerides above 4.5 mmol/L preventing calculationby Friedewald equation.Table 5: Data are mean ±SD. KJM+ and WB-control diets are based onactual intake. Baseline values are based on the mean of four 3-day foodrecords. *P<0.001 for differences between KJM+ and WB-control treatments(student's t-test for paired data)Table 6: Data are expressed as mean ±SEM, except for body weight whichis mean ±SD. Within-treatment differences (week-0 versus week-3) wereassessed by paired Student's t-test and between-treatment differences byANCOVA (GLM procedure). *Significant after adjustment of alpha level bythe Bonferroni-Hochberg procedure. Null-hypotheses were rejected only ifthe p-values were less than their corresponding α-value.

Table 7: Shows the Test Breakfast used in Example 10.

Table 8: Is a comparison of 4 studies. See Example 16.

FULL CITATIONS FOR REFERENCES REFERRED TO IN THE SPECIFICATION

-   Eliason K, Ryttig K R, Hylander B, Rossner S: A dietary fibre    supplement in the treatment of mild hypertension. A randomized,    double-blind, placebo controlled trial. J Hypertens 10: 195-199,    1992.-   American Diabetes Association (ADA): Nutrition Recommendations and    principles for people with diabetes mellitus. Diabetes care    22:S42-S43, 1999-   Anderson J W, Tietyen-Clark J: Dietary fiber: hyperlipidemia,    hypertension, and coronary heart disease. Am J Gastroenterol    81:907-919, 1986.-   Aro A, Uusitupa M, Voutilainen E, Hersio K, Korhonen T, Siitonen O:    Improved diabetic control and hypocholesterolaemic effect induced by    long-term dietary supplementation with guar gum in type 2    (insulin-independent) diabetes. Diabetologia 21:29-33, 1981.-   Arvill A, Bodin L: Effect of short-term ingestion of Konjac    glucomannan on serum cholesterol in healthy men. Am J Clin Nutr    61:585-589, 1995.-   Brown L, Rosner B, Willett W W, Sacks F M: Cholesterol-lowering    effects of dietary fiber: a meta-analysis. Am J Clin Nutr 69:30-42,    1999.-   Burt V L, Cutler J A, Higgins M, Horan M J, LaBarthe D, Whelton P,    Brown C, Rocella E J: Trends in the prevalence, awarness, treatment    and control of hypertension in the adult US population: data from    the Health Examination Surveys, 1960-1991. Hypertension 26:60-69,    1995.-   DCCT Research Group: The effect of intensive treatment of diabetes    on the development and progression of long-term complications in    insulin-dependent diabetes mellitus. The diabetes control and    complications trial. New Engl J Med 329:977-986, 1993.-   Doi K, Matsuura M, Kawara A, Baba S: Treatment of diabetes with    glucomannan Konjac mannan. Lancet 1:987-988, 1979.-   Eastwood M A, Morris E R. Physical properties of dietary fiber that    influence physiological function: a model for polymers along    gastrointestinal tract. Am J Clin Nutr 55:436-442, 1992.-   Ebihara K, Masuhara R Kiriyama S: Major determinants Plasma    glucose-flattening activity of a water-soluble dietary fiber:    effects of konjac mannan on gastric emptying and intraluminal    glucose diffusion. Nutr Reports Intl 23:1145-1156, 1981.-   Ebihara K, Schneeman B O: Interaction of bile acids, phospholipids,    cholesterol and triglycerides with dietary fibers in the small    intestine of rats. J Nutr 119:1100-1106, 1989.-   Executive Summary of the Third Report of the National Cholesterol    Education Program (NCEP) Expert Panel on Detection, Evaluation, and    Treatment of High Blood Cholesterol in Adults. JAMA; 285:2486-2497,    2001.-   Friedewald W T, Levy R I, Fridrickson D S: Estimation of plasma    low-density lipoproteins, cholesterol concentration without use of    the preparative ultracentrifuge. Clin Chem 18:499-502, 1972.-   Fruchart J C, Kora I, Cachera C, Clavey V, Duthilleul P, Moschetto    Y: Simultaneous measurements of plasma apolipoproteins A-1 and B by    electroimmunoassay. Clin Chem 28:59-62, 1982.-   Goldsmith M G, Barrett-Connor E, Edelstein S L, Wingard D L, Cobin B    T, Herrman W H: Dislipidemia and ischemic heart disease mortality    among men and women with diabetes. Circulation 89:991-997, 1994.-   Gu K, Cowie C C, Harris M I: Mortality in Adults With and Without    Diabetes in a National Cohort of the U.S. Population, 1971-1993.    Diabetes Care 21:1138-1145, 1998.-   Haffner S M, Stern M P, Hazuda H P, Rosenthal M, Knapp J A, Malina R    M: Role of obesity and fat distribution in non-insulin-dependent    diabetes mellitus in Mexican Americans and non-Hispanic whites.    Diabetes Care 9:153-161, 1986.-   Haffner S M, Stern M P, Hazuda H P, Mitchell B D, Patterson J K:    Cardiovascular risk factors in confirmed prediabetic individuals.    Does the clock for coronary heart disease start ticking before the    onset of clinical diabetes? JAMA 263:2893-8, 1990-   Haffner S M, Lehto S, Ronnemaa T, Pyorala K, Laakso M: Mortality    from coronary heart disease in subjects with type 2 diabetes and in    nondiabetic subjects with and without prior myocardial infarction. N    Engl J Med 339:229-34, 1998-   Harris M I, Flegal C M, Cowie C C, Eberhardt M S, Goldstein D E,    Little R R, Weidmeyer H-M, Byrd-Holt D D: Prevalence of diabetes,    impaired fasting glucose, and impaired glucose tolerance in U.S.    adults: The Third National Health and Nutrition Survey, 1988-1994.    Diabetes Care 21(4):518-524, 1998-   Helmrich S P, Ragland D R, Leung R W, Paffenbarger R S Jr.: Physical    activity and reduced occurrence of non-insulin-dependent diabetes    mellitus. N Engl J Med 325:147-152, 1991-   Himswarth H: Diabetes mellitus: a differentiation into    insulin-sensitive and insulin-insensitive types. Lancet i:127-130,    1936.-   Hochberg Y: A sharper Bonferroni procedure for multiple test    significance. Biometrika 75:800-802, 1988.-   Hunninghake D B, Stein E A, Dujovne C A, Harris W S, Feldman E B,    Miller V T, Tobert J A, Laskarzewski P M, Quiter E, Held J, Taylor A    M, Hoffer S, Leonard S B, Brewer B K: The efficacy of intensive    dietary therapy alone or combined with lovastatin in outpatient with    hypercholesterolemia. N Engl J Med 328:1213-1219, 1993.-   Jenkins D J, Wolever T M, Leeds A R, Gassull M A, Haisman P,    Dilawari J, Goff D V, Metz G L, Alberti K G: Dietary fibres, fibre    analogues, and glucose tolerance: importance of viscosity. Br Med J    1:1392-4, 1978.-   Jenkins D J A, Wolever T M S, Rao A V, Hegele R A, Mitchell S J,    Ransom T P P, Boctor D L, Spadafora P J, Jenkins A L, Mehling C,    Relle L K, Connelly P W, Story J A, Furumoto, E J, Corey P, Wursch    P: Effect on blood lipids of very high intakes of fibre in diets low    in saturated fat and cholesterol. N Engl J Med. 329:21-26, 1993.-   Jenkins D J, Jenkins A L, Wolever, T M, Vuksan V, Rao A V, Thompson    L U, Josse R G: Low glycemic index: lente carbohydrates and    physiological effects of altered food frequency. Am J Clin Nutr    59:706s-709s, 1994.-   Jenkins D J A, Vuksan V, Wolever T M S, Ransom T P P, Vidgen E,    Hegele R A, Leiter L, Josse R G, Abdolell, Patten R, Rao A V,    Kendall C W C, Story, J A, Boctor D L, Corey P N: Diet and    cardiovascular disease risk reduction: a place for fibre? Nutr Metab    Cardiovasc Dis 5:251-259, 1995.-   Johnson C L, Rifkind B M, Sempos C T, Carroll M D, Bachorick P S,    Briefel R R, Gordon D J, Burt V L, Brown C D, Lippel K, Cleeman J I:    Declining serum total cholesterol levels among US adults: the    National Examination Surveys. JAMA 269; 3002-3008, 1993.-   Katona G, Aganovic I, Vuksan V, Skrabalo Z: The National Diabetes    Programme in Malta: Final Report of Phases I and II. Geneva, World    Health Organization, (NCD/OND/DIAB/83.2) 1983.-   Kiriyama S, Enishi A, Yoshida A, Suhiyama N, Shimahara H:    Hypercholesterolemic activity and molecular weight of Konjac-mannan.    Nutr Reports Intl 6:231-236, 1972.-   Kiriyama S, Enishi A, Yura K: Inhibitory effect of KJM on bile acid    transport in the everted sacs from rat ileum. J Nutr 104:69-78,    1974.-   Kuzuya T, Saito T, Yoshida S: Human C-peptide immunoreactivity (CPR)    in blood and urine-Evaluation of radioimmunoassay method and its    clinical applications. Diabetologia 12:511:518, 1976-   Landin K, Holm G, Tengborn L, Smith U: Guar gum improves insulin    sensitivity, blood lipids, blood pressure, and fibrinolysis in    healthy men. Am J Clin Nutr 56:1061-1065, 1992-   Liese A D, Mayer-Davis E J, Haffner S M: Development of the insulin    resistance syndrome: An Epidemiologic Perspective. Epidemiol Rev    20:157-172, 1998-   Livesey J H, Hodgkinson S C, Roud H R, Donald R A: Effect of time,    temperature and freezing on the stability of immunoreactive LH, FSH,    TSH, growth hormone, prolactin and insulin in plasma. Clin Biochem    13:151-157, 1980-   Lloyd D, Marples J: Simple Calorimetry of glycated serum protein in    a centrifugal analyzer. Clin Chem 30:1686-1688, 1984-   McNamara J R, Schaefer E J: Automated enzymatic standardization    lipid analyses for plasma and lipid fractions. Clin Chim Acta    166:108-111, 1987-   Matsuda and DeFronzo, Diabetes Care 1999; 22:1462-70.-   Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M, Shirit A,    Fuchs Z: Hyperinsulinemia. A link between hypertension, obesity and    glucose intolerance. J Clin Invest 75:809-817, 1985.-   Morgan L M, Tredger J A, Wright J, Marks V: The effect of soluble-    and insoluble-fibre supplementation on post-prandial glucose    tolerance, insulin and gastric inhibitory polypeptide secretion in    healthy subjects. Br J Nutr 64:103-110, 1990.-   National Cholesterol Education Program: Second report of the expert    panel on detection, evaluation, and treatment of high blood    cholesterol in adults (adult treatment panel II). Circulation    89:1333-1445, 1994.-   Olson B H, Anderson S M, Becker M P, Anderson J W, Hunninghake D B,    Jenkins D J, LaRosa J C, Rippe J M, Roberts D C, Story D B,    Summerbell C D, Truswell A S, Wolever T M S, Morris D H, Fulgoni V L    3^(rd): Psyllium-enriched cereals lower blood total cholesterol and    LDL cholesterol, but not HDL cholesterol, in hypercholesterolemic    adults: results of a meta-analysis. J Nutr 127:1973-1980, 1997.-   Prosky L. Asp N G, Furda I, DeVries J W, Schweizer T F, Harland B F:    Determination of total dietary fibre in foods and food products:    collaborative study. J Assoc Off Chem 68:677-679, 1985.-   Reaven G M (1994) Syndrome X: 6 years later. J Intern Med 736:13-22,    1994.-   Remington's Pharmaceutical Sciences (Remington's Pharmaceutical    Sciences, Mack Publishing Company, Easton, Pa., USA 1985).-   Rimm E B, Ascherio A, Giovannucci E, Spiegelman D, Stampfer M J,    Willett W C: Vegetable, fruit, and cereal fiber intake and coronary    heart disease among men. JAMA 275:447-451, 1996.-   SAS Institute Inc: SAS/STAT User's guide. Version 6, 4th ed. Cary    N.C.: SAS Institute Inc, 1989.-   Salmeron J, Ascherio A, Rimm E B, Colditz G A, Spiegelman D, Jenkins    D J, Stampfer M J, Wing A L, Willett W C: Dietary fiber, glycemic    load and risk of NIDDM in men. Diabetes Care 20:545-550, 1997.-   Salmeron J, Manson J E, Stampfer M J, Colditz G A, Wing A L, Willett    W C: Dietary fiber, glycemic load and risk of non-insulin-dependent    diabetes mellitus in women. JAMA 277:472-477, 1997.-   Schaefer E J, Lichtenstein A H, Lamon-Fava S, Contois J H, Li Z,    Rasmussen H, McNamara J R, Ordovas J M: Efficacy of a National    Cholesterol Education Program Step 2 Diet in normolipidemic and    hypercholesterolemic middle-aged men and elderly men and women.    Arterioscler Thromb Vasc Biol 15:1079-1083, 1995.-   Shima K, Tabata M, Tanaka A, Kumahara Y: Effect of dietary fiber    (guar gum and konjac powder) on diabetic control. Nutr Report Intl    26:297-302, 1982.-   Shima K, Tanaka A, Ikegami H, Tabata M, Sawazaki N, Kumahara Y:    Effect of dietary fiber, glucomannan, on absorption of sulfonylurea    in man. Horm Metab Res 15:1-3, 1983.-   Salmeron J, Ascherio A, Rimm E B, Colditz G A, Spiegelman D, Jenkins    D J, Stampfer M J, Wing A L, Willett W C: Dietary fiber, glycemic    load, and risk of NIDDM in men. Diabetes Care 20:545-50, 1997.-   Salmeron J, Manson J E, Stampfer M J, Colditz G A, Wing A L, Willett    W C: Dietary fiber, glycemic load and risk of non-insulin-dependent    diabetes mellitus in women. JAMA 277:472-477, 1997.-   Savage P J: Cardiovascular complications of diabetes mellitus: what    we know and what we need to know about prevention. Ann Intern Med    124:123-126, 1996.-   Shima K, Tanaka A, Ikegami H, Tabata M, Sawazaki N, Kumahara Y:    Effect of dietary fiber, glucomannan, on absorption of sulfonylurea    in man. Horm Metab Res 15:1-3, 1983.-   Shima K, Tabata M, Tanaka A, Kumahara Y: Effect of dietary fiber    (guar gum and konjac powder) on diabetic control. Nutr Report Intl    26:297-302, 1982.-   Stamler J, Vaccaro O, Neaton J D, Wentworth D. Diabetes, other risk    factors, and 12 yr cardiovascular mortality for men in the multiple    risk factor intervention trial. Diabetes Care 16:434-444, 1993.-   Stefanick M L, Mackey S, Sheehan M, Ellsworth N, Haskell W L, Wood P    D: Effects of diet and exercise in men and postmenopausal women with    low levels of HDL cholesterol and high levels of LDL cholesterol. N    Engl J Med 339:12-20, 1998.-   Swain J F, Rouse I L, Curley C B, Sacks F M: Comparison of the    effects of oat bran and low-fibre wheat on serum lipoprotein levels    and blood pressure. N Engl J Med 322:147-152, 1990.-   Terasawa F, Tsuji K, Tsuji E, Oshima S, Suzuki S, Seki M: The    effects of konjac flour on the blood lipids in the elderly subjects.    Japan J Nutr 37:23-28, 1979.-   The Agriculture Research Services. Composition of Foods, Agriculture    Handbook No 8. Washington, D.C., US Department of Agriculture, 1992.-   The Lipid Research Clinics Population Studies Data Book. Vol. 2. The    prevalence study-nutrient intake. Washington D.C.: Government    printing office (NIH publication no. 82-2014), 1982.-   Trevisan M, Liu J, Bahsas F B, Menotti A: Syndrome X and mortality:    A Population-based Study. Am J Epidemiol 148:958-966, 1998.-   Tuomilehto J, Silvasti M, Manninen V, Uusitupa M, Aro A: Guar gum    and gemfibrozil-an effective combination in the treatment of    hypercholesterolemia. Atherosclerosis 76:71-77, 1989.-   UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive    blood-glucose control with metformin on complications in overweight    patients with type 2 diabetes: UKPDS 34. Lancet 352:854-865, 1998.-   Uuistupa M, Tuomilehto J, Karttunen P, Wolf E: Long term effects of    guar gum on metabolic control, serum cholesterol and blood pressure    levels in type 2 (non-insulin-dependent) diabetic patients with high    blood pressure. Annals Clin Res 16:126s-131s, 1984.-   Venter C S, Kruger H S, Vorster H H, Serfonrein W J, Ubbinik J B,    DeVilliers L S: The effects of dietary fibre component    konjac-glucomannan on serum cholesterol levels of    hypercholesterolemic subjects. Human Nutr: Food Sci and Nutr    41F:55-61, 1987.-   Venter C S Vorster H H, Cummings J H: Effects of dietary propionate    on carbohydrate and lipid metabolism in healthy volunteers. Am J    Gastroenterol 85:549-553, 1990.-   Vuksan V, Jenkins D J A, Spadafora P, Sievenpiper J L, Owen R,    Vidgen E, Brighenti F, Josse R G, Leiter L A, Bruce-Thompson C:    Konjac-mannan (glucomannan) improves glycemia and other associated    risk factors for coronary heart disease in type 2 diabetes: A    randomized controlled metabolic trial. Diabetes Care 22:913-19,    1999.-   Vuksan V, Sievenpiper J L, Koo V Y Y, et al. American ginseng    reduces postprandial glycemia in nondiabetic and diabetic    individuals. Arch Intern Med 2000; 160:1009-13.-   Vuksan V, Stavro M P, Sievenpiper J L, Beljan-Zdravkovic U, Leiter L    A, Josse R G, Zheng Xu. Similar postprandial glycemic reductions    with escalation of dose and administration time of American ginseng    in type 2 diabetes. Diabetes Care 2000; 23:1221-6.-   Vuksan V, Stavro M P, Sievenpiper J L, et al. American ginseng    improves glycemia in individuals with normal glucose tolerance:    Effect of dose and time escalation. J Am Coll Nutr, 2000;    19:738-744.-   Vuksan V, Sievenpiper J L, Xu Z, et al. American ginseng (Panax    quinquefolius L.) attenuates postprandial glycemia in a time, but    not dose, dependent manner in healthy individuals. Am J Clin Nutr,    in press.-   Vuksan V, Xu Z, Jenkins A L, Beljan-Zdravkovic U, Sievenpiper J L,    Leiter L A, Josse R G, Stavro M P. American Ginseng improves    long-term glycemic control in Type 2 diabetes: Double-Blind Placebo    Controlled Crossover Trial. American Diabetes Association Annual    Meeting, Diabetes 2000; 49 (Suppl 1):A95.-   Vuksan V, Sievenpiper J L. The variable effects of whole-leaf    digitalis is a paradigm of the glycemic effects of ginseng-Reply.    Arch Intern Med, 2000; 160:3330-1.-   Warnick G R, Benderson J, Albers J J: Dextran sulfate-Mg⁺²    precipitation procedure for quantitation of high-density lipoprotein    cholesterol. Clin Chem 28: 1379-1388, 1982.-   Wei M, Gaskill S P, Heffner S M, Ster M P: Effects of diabetes and    level of glycemia on all-cause and cardiovascular mortality: The San    Antonio Heart Study. Diabetes Care 21(7):1167-1172, 1998.-   Wing M, Gaskill S P, Haffner S M, Stern M P: Effects of Diabetes and    Level of Glycemia on All-Cause and Cardiovascular Mortality.    Diabetes Care 21:1167-1172, 1998.-   Wolever T M, Jenkins D J A, Vuksan V, Jenkins A L, Wong G S, Josse R    G: Beneficial effect of low-glycemic index diet in overweight NIDDM    subjects. Diabetes Care 15(4):562-564, 1992.-   World Health Organization Diabetes Mellitus: Report of the World    Health Organization Study Group. Technical report No. 727:9-15,    1985.-   Wood P J: Physicochemical properties and physiological effects of    the (1-3)(1-4)-beta-D-glucan from oats. Adv Exp Med Biol 270:119-27,    1990.

1-43. (canceled)
 44. A composition of matter for reducing blood glucosecomprising ginseng.
 45. The composition of claim 44 wherein the ginsengis an extract of ginseng.
 46. The composition according to claim 44wherein the ginseng comprises a ratio of diols/triols of greater thanabout 1.5.
 47. The composition according to claim 44 wherein thecomposition is formulated into a liquid, powder or food.
 48. A methodfor the treatment or prevention of a disorder which benefits fromreducing blood glucose in an animal comprising administering to theanimal in need thereof a sufficient amount of ginseng.
 49. The methodaccording to claim 48 wherein the ginseng is an extract of ginseng. 50.The method according to claim 48 wherein the ginseng is administeredbefore a meal or with a meal.
 51. The method according to claim 48wherein administration before the meal occurs from about 1 to about 180minutes before the meal.
 52. The method according to claim 48 whereinthe amount of ginseng is at least about 1000 mg per administration. 53.The method according to claim 48 wherein the ginseng comprises a ratioof diols/triols of greater than about 1.5.
 54. The method according toclaim 48 wherein the ginseng is administered as a food, a powder, or aliquid.
 55. The method according to claim 48 wherein the ginseng isAmerican ginseng.
 56. The method according to claim 48 wherein thedisorder which benefits from reducing blood glucose is diabetes, heartdisease, or syndrome X.
 57. The method according to claim 48 wherein themethod increases insulin sensitivity in an animal.
 58. The methodaccording to claim 48 wherein the disorder comprises type 2 diabetes.59. The method according to claim 48 wherein the method reduces systolicblood pressure, blood cholesterol or lipids.
 60. The method according toclaim 48 wherein the method increases insulin secretion.
 61. The methodaccording to claim 48 wherein the animal comprises a human.
 62. A methodfor the treatment or prevention of a disorder which benefits fromreducing blood glucose in an animal comprising administering to theanimal a sufficient amount of a composition comprising a konjac mannanmixture and ginseng.